44
Go with the flow
P
lace your hand over your heart. Now place it over
your liver. Next over your appendix. Surely you put
your hand first on the left side of your chest, then on
your right side just under your ribs, and finally on the
right side of your lower abdomen. But in Chapter 31 you
learned that vertebrates (including you) are bilaterally
symmetrical (left arm/right arm, left kidney/right kidney,
and so on). Clearly, however, our bilateral symmetry is
not absolute.
Some of our internal organs—including the heart, liver,
appendix, stomach, and the lobes of the lungs—are oriented differently with respect to the left and right sides of
the body. How does a developing embryo know which
side is left and which is right?
Clues to answering this question came from the fact
that in about 1 out of every 7,000 people, the arrangement of the internal organs is reversed, a condition
known as situs inversus, Latin for “location inverted.” This
developmental difference arises when the very early
embryo goes from being a single layer of cells to multiple
layers of cells.
As you will learn in this chapter, to get from a single
layer of cells to the next stage with two layers of cells, a
pore or slit forms as cells in one area of the embryo migrate inward from the surface. Other cells from the surface migrate toward and through this opening to take up
positions underneath. The place where the inward movement of cells starts is called the node. Cells of the node
have motile cilia that sweep extracellular fluid
through the opening.
Cells bordering the node also have one nonmotile
cilium each—a primary cilium. When the primary
cilia are bent by the flow of extracellular fluid, they
initiate signaling cascades that determine the pattern of internal organ development. Since the fluid
driven by the motile cilia tends to flow from right to
left, the signaling cascades are not expressed symmetrically, and this initiates the left–right organization of organ development.
Among individuals carrying a mutation that eliminates motility of the nodal cilia, half have the normal
orientation of the internal organs and half have situs
inversus. Most people with this condition lead normal, healthy lives. They may not even know about it
Go with the Flow The internal organs of humans are
not all symmetrical, and some individuals are born with
the mirror-image pattern of what is seen in most people—
a condition called situs inversus. The left–right asymmetry
of the internal organs is initiated by asymmetrical stimulation of primary cilia at a very early stage in development.
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© 2010 Sinauer Associates, Inc.
CHAPTER OUTLINE
44.1 How Does Fertilization Activate Development?
44.2 How Does Gastrulation Generate Multiple Tissue
Layers?
44.3 How Do Organs and Organ Systems Develop?
44.4 How is the Growing Embryo Sustained?
44.5 What Are the Stages of Human Development?
44.1
When Sperm Meet Egg Development begins with the fertilization of an egg by a sperm. Once one sperm fuses with the
egg, all other sperm are blocked. An animal egg typically is
much larger than the sperm; the egg cytoplasm is loaded with
informational molecules and nutrients that will direct development and nourish the growing embryo.
unless a routine physical exam reveals that the organs
are not where they should be.
As frequently happens in biology, we just pushed the
question back one more step. Why do the nodal cilia
beat in such a way that the extracellular fluid flows from
right to left? The root cause of this asymmetry likely originates in some of the early cell divisions of the fertilized
egg. The fertilized egg goes through an initial series of
cell divisions that subdivide the egg cytoplasm into a
mass of undifferentiated cells. Although this mass of
cells shows no hints of the eventual body plan, an uneven distribution of molecules from the cytoplasm of the
fertilized egg can provide information that directs the
fates of cells and sets up the body plan.
IN THIS CHAPTER we will see how a single cell becomes a multicellular animal through orderly cell movements that create multiple layers and set up cell–cell interactions. The regional and temporal differences in gene
expression that control cell differentiation, described in
Chapters 19 and 20, lead to the emergence of the body plan
of the animal. We will discuss these early developmental
steps in four organisms that have been studied extensively:
sea urchins, frogs, chickens, and humans.
How Does Fertilization Activate
Development?
Fertilization is the joining of sperm and egg. You might therefore think of it as the event that begins development. Keep two
things in mind, however. First, in animals that reproduce asexually, development proceeds without fertilization. And second,
in animals where fertilization does occur, it is preceded by critical events in the maturing egg that will influence subsequent
development. Thus, in studying fertilization we are really asking how it activates or restarts multicellular development in sexually reproducing animals.
Fertilization does far more than just restore a full diploid
complement of maternal and paternal genes. The fusion of
sperm and egg plasma membranes accomplishes several things:
• It sets up blocks to the entry of additional sperm.
• It stimulates ion fluxes across the egg membrane.
• It changes the egg’s pH.
• It increases egg metabolism and stimulates protein synthesis.
• It initiates the rapid series of cell divisions that produce a
multicellular embryo.
Section 43.2 described the mechanisms of fertilization. Here we
take a closer look at the cellular and molecular interactions of
sperm and egg that initiate the first steps of development.
The sperm and the egg make different contributions
to the zygote
In most species, eggs are much larger than sperm. Egg cytoplasm is well stocked with organelles, nutrients, and a variety
of molecules, including transcription factors and mRNAs. The
sperm is little more than a DNA delivery vehicle. Nearly everything the embryo needs during its early stages of development
comes from the mother. In addition to providing its haploid nucleus, the sperm makes another important contribution to the
zygote in most species—a centriole.
The centriole becomes the centrosome of the zygote, which
organizes the mitotic spindles for subsequent cell divisions (see
Figure 11.10). The centriole is also the origin of the primary cilia
of cells, which are important in cell signaling, as we saw in the
opening story about situs inversus.
Cytoplasmic factors in the egg play important roles in setting up the signaling cascades that orchestrate the major events
of development: determination, differentiation, and morphogenesis.
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924
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ANIMAL DEVELOPMENT
Rearrangements of egg cytoplasm set the stage for
determination
The unique attributes of amphibian eggs make them ideal models for illustrating how rearrangements of egg cytoplasm set the
stage for determination. The molecules in the cytoplasm of the
amphibian egg are not homogeneously distributed. The entry
of the sperm into the egg stimulates rearrangements of the egg
cytoplasm that introduce additional organization to the egg cytoplasm. This rearrangement establishes the polarity of the zygote, and when cell divisions begin, the informational molecules that will guide development are not divided equally
among daughter cells.
Rearrangement of egg cytoplasm following fertilization is
easily observed in some frog species because of pigments in the
cytoplasm. The nutrients in an unfertilized frog egg are dense
yolk granules that are concentrated by gravity in the lower half
of the egg, called the vegetal hemisphere. The haploid nucleus
of the egg is located at the opposite end, in the animal hemisphere. The outermost (cortical) cytoplasm of the animal hemisphere is heavily pigmented, and the underlying cytoplasm has
more diffuse pigmentation. The vegetal hemisphere is not pigmented. Because of these differences, it is easy to observe how
the cytoplasm is rearranged when a frog egg is fertilized.
The frog egg is radially symmetrical. You can turn it on its
vegetal–animal pole axis, and all sides are the same. Spermbinding sites are localized on the surface of the animal hemisphere, so that is where the sperm enters the egg. When a sperm
enters the egg, bilateral symmetry is imposed by creating an anterior–posterior axis. Cortical cytoplasm rotates toward the site
of sperm entry. This rotation brings different regions of cytoplasm into contact with each other on opposite sides of the egg,
producing a band of diffusely pigmented cytoplasm on the side
opposite the site of sperm entry. This band, called the gray crescent, marks the location of important developmental events in
some species of amphibians (Figure 44.1).
The one non-nuclear organelle that the sperm contributes to
the egg—the centriole—initiates the cytoplasmic reorganization
revealed by the appearance of the gray crescent. The centriole
organizes the microtubules in the vegetal hemisphere cytoplasm
into a parallel array that guides the movement of the cortical
cytoplasm. These microtubules also appear to be directly responsible for movement of specific organelles and proteins, because these organelles and proteins move from the vegetal
(A) Fertilization Animal pole
Egg
b-catenin (orange)
is distributed
throughout cytoplasm.
Sperm
GSK-3 (blue), which targets
b-catenin for degradation,
is also found throughout
cytoplasm.
Vegetal pole
A protein that inhibits
GSK-3 is contained in
vegetal pole vesicles.
(B) Cortical rotation
Ventral
(V)
Dorsal
(D)
Vesicles in the vegetal
pole move on microtubule tracks to the side
opposite sperm entry.
(C) Dorsal enrichment
inhibitor
The vesicles release
GSK-inhibiting protein…
V
D
(D) Dorsal inhibition
of GSK-3 V
…so GSK-3 does not
degrade b-catenin
on the dorsal side…
D
…but does degrade
it on the ventral side.
Animal
cortical
cytoplasm
(pigmented)
Animal
pole (A)
The cortical cytoplasm
rotates relative to the
inner cytoplasm.
(E) Dorsal enrichment
of β-catenin
A
Inner
cytoplasm
Sperm
entry
point
Vegetal
pole (V)
V
Vegetal
cortical
cytoplasm
(unpigmented)
V
The gray crescent
is created by the
rotation.
44.1 The Gray Crescent Rearrangement of the cytoplasm of frog eggs
after fertilization creates the gray crescent.
Thus there is a higher
b-catenin concentration
in the dorsal cells of the
early embryo.
D
44.2 Cytoplasmic Factors Set Up Signaling Cascades
Cytoplasmic movement changes the distributions of critical
developmental signals. In the frog zygote, the interaction of the
protein kinase GSK-3, its inhibitor, and the protein β-catenin are
crucial in specifying the dorsal–ventral axis of the embryo.
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any form without express written permission from the publisher.
© 2010 Sinauer Associates, Inc.
44.1
hemisphere to the gray crescent region even faster than the cortical cytoplasm rotates.
The movement of cytoplasm, proteins, and organelles
changes the distribution of critical developmental signals. A key
transcription factor in early development is β-catenin, which
is produced from maternal mRNA (mRNA produced and stored
in the egg while it was maturing in the ovary). Beta-catenin is
found throughout the egg cytoplasm. Also present throughout
the egg cytoplasm is a protein kinase called glycogen synthase
kinase-3 (GSK-3), which phosphorylates and thereby targets
β-catenin for degradation. An inhibitor of GSK-3 is segregated
in the vegetal cortex of the egg. After sperm entry, this inhibitor
is moved along microtubules to the gray crescent, where it prevents the degradation of β-catenin. As a result, the concentration of β-catenin is higher on the dorsal than on the ventral side
of the developing embryo (Figure 44.2).
Beta-catenin plays a major role in the cell–cell signaling cascade that begins the process of cell determination and the formation of the embryo. But before cell–cell signaling can occur,
multiple cells must be in place. Let’s turn to the early series of
cell divisions that transform the zygote into a multicellular
embryo.
(A) Complete cleavage (frog)
|
HOW DOES FERTILIZATION ACTIVATE DEVELOPMENT?
925
Cleavage repackages the cytoplasm
Transformation of the diploid zygote into a mass of cells occurs
through a rapid series of cell divisions called cleavage. Because
the cytoplasm of the zygote is not homogeneous, these first cell
divisions result in the differential distribution of nutrients and
cytoplasmic determinants in the early embryo.
In most animals, cleavage proceeds with rapid DNA replication and mitosis but with no cell growth and little gene expression. The embryo becomes a solid ball of smaller and smaller
cells. Eventually, this ball forms a central fluid-filled cavity called
a blastocoel, at which point the embryo is called a blastula. Its
individual cells are called blastomeres. The pattern of cleavage
in different species influences the form of their blastulas.
• Complete cleavage occurs in most eggs that have little yolk
(stored nutrients). In this pattern, early cleavage furrows divide the egg completely and the blastomeres are of similar
size. The frog egg undergoes complete cleavage, but because its vegetal pole contains more yolk, the division of
the cytoplasm is unequal and the blastomeres in the animal
hemisphere are smaller than those in the vegetal hemisphere (Figure 44.3A).
Animal pole
Vegetal cells have incorporated
yolk and are thus larger than
the animal cells in the 16-cell
embryo.
The planes of the second cleavage
are displaced only slightly by
yolk in the cytoplasm.
The embryo forms as a blastodisc
that sits on top of the yolk mass.
(B) Incomplete cleavage (zebrafish)
In birds and fishes, cleavage
furrows do not penetrate the
large yolk mass.
(C) Superficial cleavage (Drosophila) 1 Mitosis (nuclear division)
occurs without cell division.
3 The nuclei migrate to the inner
edge of the plasma membrane.
Nucleus
2 A syncitium—a single cell
with many nuclei—is produced.
4 Cellularization occurs,
creating a blastoderm
44.3 Some Patterns of Cleavage Differences in patterns
of early embryonic development reflect differences in the way
the egg cytoplasm is organized. (A) The frog is a model organism representing complete cleavage in these scanning electron
micrographs. (B) SEMs of zebrafish embryos illustrate incomplete cleavage, in which the large yolk mass limits the planes of
cleavage. (C) Nuclear staining reveals the syncitial nuclei characteristic of the early embryo of a fruit fly. These nuclei migrate
to the periphery. Cleavage furrows then move inward to separate the nuclei into individual cells, forming the blastoderm.
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CHAPTER 44
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ANIMAL DEVELOPMENT
• Incomplete cleavage occurs in many species in which the
egg contains a lot of yolk and the cleavage furrows do not
penetrate it all. Discoidal cleavage is a type of incomplete
cleavage common in fishes, reptiles, and birds, the eggs of
which contain a dense yolk mass. The embryo forms as a
disc of cells, called a blastodisc, that sits on top of the yolk
mass (Figure 44.3B).
• Superficial cleavage is a variation of incomplete cleavage
that occurs in insects such as the fruit fly (Drosophila). Early
in development, cycles of mitosis occur without cell division, producing a syncytium—a single cell with many nuclei
(Figure 44.3C). The nuclei eventually migrate to the periphery of the egg, after which the plasma membrane of the egg
grows inward, partitioning the nuclei into individual cells
surrounding a core of yolk.
The positions of the mitotic spindles during cleavage are not
random but are defined by cytoplasmic factors produced from
the maternal genome and stored in the egg (see Section 19.4).
The orientation of the mitotic spindles can determine the planes
of cleavage and the arrangement of the blastomeres.
In complete cleavage, if the mitotic spindles of successive cell
divisions form parallel or perpendicular to the animal–vegetal
axis of the zygote, a pattern of radial cleavage occurs as seen
in the frog: the first two cell divisions are parallel to the animal–vegetal axis and the third is perpendicular to it (see Figure
44.3A). Spiral cleavage results when the mitotic spindles are at
oblique angles to the animal–vegetal axis. In spiral cleavage,
each new cell layer is shifted to the left or right, depending on
the orientation of the mitotic spindles. Most mollusks have spiral cleavage, reflected in some species by a coiling shell pattern (as seen in snails).
(A)
Parallel
plane
A
Plane of first
cell division
Perpendicular
plane
Several features of early cell divisions in placental mammals
(eutherians) are so different from those seen in other animal
groups that some biologists think it is inappropriate to call it
cleavage. But whether you call it cleavage or not, it is still the
sequence of early cell divisions that produces a body of undifferentiated cells that will become the embryo. This process in
mammals is very slow. Cell divisions are 12 to 24 hours apart,
compared with tens of minutes to a few hours in non-mammalian species. Also, the cell divisions of mammalian blastomeres are not in synchrony with each other. Because the blastomeres do not undergo mitosis at the same time, the number
of cells in the embryo does not increase in the regular (2, 4, 8,
16, 32, etc.) progression typical of other species.
The pattern of mammalian cleavage is rotational: the first cell
division is parallel to the animal–vegetal axis, yielding two blastomeres. In the second cell division, those two blastomeres divide at right angles to one other: one divides parallel to the animal–vegetal axis, while the other divides perpendicular to it
(Figure 44.4A).
Another unique feature of the slow, rotational mammalian
cleavage is that gene products expressed during cleavage play
roles in cleavage. In animals such as sea urchins and frogs, gene
transcription does not occur in the blastomeres, and cleavage is
therefore directed exclusively by molecules that were present
in the egg before fertilization.
As in other animals that have complete cleavage, the early cell
divisions in a mammalian zygote produce a loosely associated
ball of cells. After the 8-cell stage, however, the behavior of the
mammalian blastomeres changes. They change shape to maximize their surface contact with one another, form tight junctions,
and become a compact mass of cells (Figure 44.4B).
At the transition from the 16- to the 32-cell stage (the fourth
division), the cells separate into two groups. The inner cell mass
will become the embryo, while the surrounding outer cells become an encompassing sac called the trophoblast. Trophoblast
cells secrete fluid, creating a cavity—the blastocoel—with the in-
44.4 Becoming a Blastocyst (A) Mammals have rotational cleavage, in which the plane of the first
cleavage is parallel to the animal–vegetal (A–V) axis, but the second cell division involves two planes (beige)
at right angles to each other. (B) Scanning electron micrographs show that asynchronous cell division
results in an asymmetrical blastocyst at about the 32-cell stage. (C) Seen in cross section under a light
microscope, the mammalian blastocyst consists of an inner cell mass adjacent to a fluid-filled blastocoel
and surrounded by trophoblast cells.
V
(B)
8-cell stage
Early cell divisions in mammals are unique
(C)
16-cell stage
32-cell stage
Blastocyst
(cross section)
Trophoblast
(outer cells)
Blastocoel
The inner cell mass will
form the embryo.
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any form without express written permission from the publisher.
© 2010 Sinauer Associates, Inc.
44.1
16–32 cells (3–4 days
postfertilization)
Implantation of blastocyst
(6–7 days postfertilization)
Ovary
2–4 cells (2 days
postfertilization)
Site of
fertilization
Uterus
Cervix
Vagina
Human embryo at 9 days
Wall of uterus
Developing placenta
Inner cell
mass
(embryo)
Amnion
Hypoblast
Emerging
chorionic
villus
Epiblast
Trophoblast
Blastocoel
Blood
vessel
Endometrium
|
HOW DOES FERTILIZATION ACTIVATE DEVELOPMENT?
927
44.5 A Human Blastocyst at Implantation Adhesion molecules and
proteolytic enzymes secreted by trophoblast cells allow the blastocyst to
burrow into the endometrium. Once the blastocyst is implanted in the wall
of the uterus, the trophoblast cells send out numerous projections—the
chorionic villi—which increase the embryo’s area of contact with the
mother’s bloodstream.
bryo, a connection develops between the circulatory systems of
the embryo and the mother. As we will see later in this chapter, the structures that provide this connection are the placenta
and the umbilical cord. Thus, the mammalian blastocyst must
produce both the embryo (from the inner cell mass) and its support structures (from the trophoblast).
Fertilization in mammals occurs in the upper reaches of the
mother’s oviduct, and cleavage occurs as the zygote travels
down the oviduct to the uterus. When the blastocyst arrives in
the uterus, the trophoblast adheres to the lining of the uterus
(the endometrium), beginning the process of implantation. In humans, implantation begins about 6 days after fertilization and
is aided by adhesion molecules and enzymes secreted by the
trophoblast (Figure 44.5).
As the blastocyst moves down the oviduct to the uterus, it
must not embed itself in the oviduct (Fallopian tube) wall, or
the result will be an ectopic, or tubal, pregnancy—a very dangerous condition. Early implantation is prevented by the zona pellucida, which surrounded the egg and remains around the
cleaving ball of cells (see Section 43.2). At about the time the
blastocyst reaches the uterus, it hatches from the zona pellucida,
and implantation can occur.
Specific blastomeres generate specific tissues
and organs
ner cell mass at one end (Figure 44.4C). At this stage, the mammalian embryo is called a blastocyst, distinguishing it from the
blastulas of other animal groups.
Why is mammalian cleavage so different? A key factor is that
mammalian eggs contain no yolk and must derive all nutrients
from the mother. Mammals are viviparous: the embryo develops
within the uterus of the mother. To support the developing em-
Animal pole
Ectoderm will
form epidermal
layer of skin.
The neural ectoderm
(midline) will form the
nervous system.
The gray crescent is
the site where major
cell movement will
begin. (See Figure
44.1)
Endoderm will form the
lining of the gut, the liver,
and the lungs.
Vegetal pole
Mesoderm will form muscle,
bone, kidneys, blood, gonads,
and connective tissues.
Cleavage results in a repackaging of the egg cytoplasm into a
large number of small cells surrounding the fluid-filled blastocoel. Except in mammals, little cell differentiation and little if
any gene expression occur during cleavage. Nevertheless, cells
in different regions of the blastula possess different complements of the nutrients and cytoplasmic determinants that were
present in the egg.
The blastocoel prevents cells from different regions of the
blastula from coming into contact and interacting, but that will
soon change. During the next stage of development, the cells of
the blastula will move around and come into new associations
with one another, communicate instructions to one another, and
begin to differentiate. In many animals, these movements of the
blastomeres are so regular and well orchestrated that it is possible to label a specific blastomere with a dye and identify the
tissues and organs that form from its progeny. Such labeling experiments produce fate maps of the blastula (Figure 44.6).
Blastomeres become determined—committed to specific
fates—at different times in different species. In some species,
44.6 Fate Map of a Frog Blastula Colors indicate the portions of the
blastula that will form the three germ layers and subsequently the frog’s
tissues and organs.
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928
CHAPTER 44
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ANIMAL DEVELOPMENT
such as roundworms, the fates of blastomeres are restricted as
early as the two-cell stage. If one of these blastomeres is experimentally removed, a particular portion of the embryo will not
form. This type of development has been called mosaic development because each blastomere seems to contribute a specific
set of “tiles” to the final “mosaic” that is the adult animal.
In contrast to mosaic development, the loss of some cells during cleavage in regulative development does not affect the developing embryo, because the remaining cells compensate for
the loss. Regulative development is typical of many vertebrate
species, including humans. The pluripotent cells of the mammalian blastocyst (the inner cell mass) are known as embryonic
stem cells and are the subject of much research, particularly because of their therapeutic potential (see Section 19.2).
If some blastomeres can change their fate to compensate for
the loss of other cells during cleavage and blastula formation,
can those cells form an entire embryo? To a certain extent, yes.
During cleavage or early blastula formation in mammals, for
example, if the blastomeres are physically separated into two
groups, both groups can produce complete embryos. Since the
two embryos come from the same zygote, they will be monozygotic twins—genetically identical.
Non-identical twins occur when two separate eggs are fertilized by two separate sperm. Thus, while identical twins are
always of the same sex, non-identical twins have a 50 percent
chance of being the same sex. In about 1 out of 50,000 human
pregnancies, genetic or environmental factors cause the inner
cell mass to split partially. The result is twins that are conjoined
at some point on their bodies, usually sharing some of their
organs and limbs.
44.1 RECAP
The egg is stocked with nutrients and informational
molecules that power and direct the early stages of
development. Fertilization activates the egg and
stimulates rearrangement of the cytoplasm, setting
up the body axes and positional information that
initiate signaling cascades, which control determination and differentiation.
•
Explain how β-catenin becomes concentrated in only
certain blastomeres. See p. 925 and Figure 44.2
•
In general terms, describe the difference between
complete and incomplete cleavage. See pp. 925–926
and Figure 44.3
•
What does a fate map tell us? How are fate maps
constructed? See pp. 927–928 and Figure 44.6
Of the next stage of development—gastrulation—the developmental biologist Louis Wolpert once said, “It is not birth, marriage, or death, but gastrulation which is the most important
time in your life.” During gastrulation, cell movements create
new cell-to-cell contacts, which in turn sets up signaling cascades. Signaling cascades initiate the differentiation of cells and
tissues and set the stage for the emergence of the body plan.
44.2
How Does Gastrulation Generate
Multiple Tissue Layers?
The blastula is typically a fluid-filled ball of cells. How does this
simple ball of cells become an embryo made up of multiple
tissue layers with head and tail ends and dorsal and ventral
sides? Gastrulation is the process whereby the blastula is transformed by massive movements of cells into an embryo with
multiple tissue layers and distinct body axes. The resulting spatial relationships between tissues make possible the inductive
interactions between cells that trigger differentiation and organ
formation (see Figure 19.10).
During gastrulation, three germ layers (also called cell layers
or tissue layers) form (see Figure 44.6):
• The endoderm is the innermost germ layer, created as some
blastomeres move to the inside of the embryo. The endoderm gives rise to the lining of the digestive tract, respiratory tract, pancreas, and liver.
• The ectoderm is the outer germ layer, formed from those
cells remaining on the outside of the embryo. The ectoderm
gives rise to the nervous system, including the eyes and
ears; and to the epidermal layer of the skin and structures
derived from skin, such as hair, feathers, nails or claws,
sweat glands, oil glands, and even teeth and other tissues
of the mouth.
• The mesoderm is the middle layer and is made up of cells
that migrate between the endoderm and the ectoderm. The
mesoderm contributes tissues to many organs, including
the heart, blood vessels, muscles, and bones.
Some of the most interesting and important challenges in animal development have dealt with two related questions: what
directs the cell movements of gastrulation, and what is responsible for the resulting patterns of cell differentiation and organ
formation? Scientists have made significant progress in answering both these questions at the molecular level. In the following
discussion, we will begin with sea urchin gastrulation because
it is the simplest to conceptualize in spatial terms. We will then
describe the more complex pattern of gastrulation in frogs,
which in turn will help elucidate the still more complex patterns
in reptiles, birds, and mammals.
Invagination of the vegetal pole characterizes
gastrulation in the sea urchin
The sea urchin blastula is a hollow ball of cells only one cell
thick. The end of the blastula stage is marked by slowing of the
rate of mitosis; the beginning of gastrulation is marked by a flattening of the vegetal hemisphere (Figure 44.7). Some cells at the
vegetal pole bulge into the blastocoel, break away from neighboring cells, and migrate into the cavity. These cells become
mesenchyme —cells of the middle germ layer, the mesoderm.
Mesenchymal cells are not organized in tightly packed sheets
or tubes like epithelial cells are; they act as independent units,
migrating into and among the other tissue layers.
The flattening at the vegetal pole results from changes in the
shape of individual blastomeres. These cells, which are origi-
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any form without express written permission from the publisher.
© 2010 Sinauer Associates, Inc.
44.2
1 The vegetal
pole of the
blastula
flattens.
2 Some cells change
shape and move
inward to form the
archenteron.
|
HOW DOES GASTRULATION GENERATE MULTIPLE TISSUE LAYERS?
3 Other cells break
free, becoming
primary
mesenchyme.
Animal
hemisphere
4 More cells break free,
forming secondary
mesenchyme. Thin
extensions of these
cells (filopodia) attach to
the overlying ectoderm.
5 The archenteron is
929
6 The mouth will
elongated by contraction
of mesenchymal filopodia
and cell rearrangement.
form where the
archenteron
meets ectoderm.
Secondary
mesenchyme
Ectoderm
Endoderm
Archenteron
Vegetal
hemisphere
Primary
mesenchyme
Blastopore
7 The blastopore will form the
44.7 Gastrulation in Sea Urchins During gastrulation, cells move to new positions
and form the three germ layers from which differentiated tissues develop.
anus of the mature animal.
yo u r B i oPort al.com
GO TO
Animated Tutorial 44.1 • Gastrulation
nally rather cuboidal, become wedge-shaped, with smaller
outer edges and larger inner edges. As a result, the vegetal pole
bulges inward, or invaginates, as if someone were poking a finger into a hollow ball (see Figure 44.7). The invaginating cells
become endoderm and form the primitive gut, called the
archenteron. At the tip of the archenteron, more cells enter the
blastocoel to form more mesoderm.
Changes in cell shapes cause the initial invagination of the
archenteron, but eventually it is pulled by the mesenchyme cells.
These cells, attached to the tip of the archenteron, send out extensions called filopodia that adhere to the overlying ectoderm.
When the filopodia contract, they pull the archenteron toward
the ectoderm at the opposite end of the embryo from where the
invagination began. The mouth of the animal forms where the
archenteron makes contact with this overlying ectoderm. The
opening created by the invagination of the vegetal pole is called
the blastopore; it will become the anus of the animal.
What mechanisms control the various cell movements of sea
urchin gastrulation? The immediate answer is that specific properties of particular blastomeres change. For example, some vegetal cells change shape and bulge into the blastocoel, and these
cells become mesenchyme. Once they lose contact with their
neighboring cells on the surface of the blastula, they send out
filopodia that then move along an extracellular matrix of proteins laid down by the cells lining the blastocoel.
A deeper understanding of gastrulation requires that we discover the molecular mechanisms whereby different blastomeres
develop different properties. Cleavage systematically divides
up the cytoplasm of the egg. The sea urchin blastula at the 64cell stage is radially symmetrical, but it has polarity, as described
in Section 19.4. It consists of tiers of cells. As in the frog blastula,
the top is the animal pole and the bottom the vegetal pole.
If different tiers of blastula cells are separated, they show different developmental potentials; only cells from the vegetal pole
are capable of initiating the development of a complete larva
(see Figure 19.8). It has been proposed that these differences are
due to uneven distribution of various transcriptional regulatory
proteins in the egg cytoplasm. As cleavage progresses, these
proteins end up in different groups of cells. Therefore, specific
sets of genes are activated in different cells, determining their
different developmental capacities.
Let’s turn now to gastrulation in the frog, in which several
key signaling molecules have been identified.
Gastrulation in the frog begins at the gray crescent
Amphibian blastulas have considerable yolk and are more than
one cell thick; therefore, gastrulation is more complex in amphibians than in sea urchins. Variation is considerable among
different species of amphibians, but in this brief account we will
use results from studies done on different species to produce a
generalized picture of amphibian development.
Amphibian gastrulation begins when certain cells in the gray
crescent region change their shapes and cell adhesion properties. These cells bulge inward toward the blastocoel while they
remain attached to the outer surface of the blastula by slender
necks. Because of their shape, these cells are called bottle cells.
Bottle cells mark the spot where the dorsal lip of the blastopore will form (Figure 44.8). As the bottle cells move inward,
the dorsal lip is created, and a sheet of cells moves over it into
the blastocoel. This process is called involution. One group of involuting cells is the prospective endoderm; these cells form the
primitive gut, or archenteron. Another group will move between the endoderm and the outermost cells to form the mesoderm. These rearrangements are due to changes in cell properties called convergent extension. The cells elongate in the
direction of movement, but they also intercalate (move in between each other). If they just elongated, the migrating group
of cells would become much narrower; by intercalating, they
maintain the width of the migrating cell group.
As gastrulation proceeds, cells from the animal hemisphere
flatten and move toward the site of involution in a process called
epiboly. The blastopore lip widens and eventually forms a com-
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930
CHAPTER 44
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ANIMAL DEVELOPMENT
Animal pole
Blastocoel
1 Gastrulation begins
when cells in the region
of the gray crescent
move inward, forming
the dorsal lip of the
future blastopore.
Bottle cells
Dorsal lip of
blastopore
Vegetal pole
Blastocoel
Bottle cells
Archenteron
begins to
form
2 Cells of the animal
Dorsal lip
pole spread out,
pushing surface cells
below them toward
and across the
dorsal lip. These cells
involute into the
interior of the
embryo, where they
form the endoderm
and mesoderm.
Archenteron
Mesoderm
Dorsal lip
Blastocoel
displaced by
mesoderm
Endoderm
Archenteron
(future digestive
tract)
3 Involution creates the
archenteron and
destroys the
blastocoel. The
blastopore lip forms
a circle, with cells
moving to the interior
all around the
blastopore; the yolk
plug is visible through
the blastopore.
a dorsal–ventral and anterior–posterior organization. Most importantly, the fates of specific regions of the endoderm, mesoderm, and ectoderm have been determined. The beautiful experiments revealing how determination takes place in the
amphibian embryo are an old but exciting story.
Ectoderm
Mesoderm
(notochord)
Dorsal lip
Yolk plug
Ventral lip of
blastopore
44.8 Gastrulation in the Frog Embryo The colors in this diagram are
matched to those in Figure 44.6, the frog fate map.
plete circle surrounding a “plug” of yolk-rich cells. As cells continue to move inward through the blastopore, the archenteron
grows, gradually displacing the blastocoel.
As gastrulation comes to an end, the amphibian embryo consists of three germ layers: ectoderm on the outside, endoderm
on the inside, and mesoderm in between. The embryo also has
The dorsal lip of the blastopore organizes
embryo formation
In the early 1900s, the German biologist Hans Spemann was
studying the development of salamander eggs. He was interested in finding out whether the nuclei of blastomeres remain
capable of directing the development of complete embryos.
With great patience and dexterity, he formed loops from single
hairs taken from a baby (in fact, his daughter) and tied them
around fertilized eggs along the plane of the first cell division,
effectively dividing the eggs in half, with the nucleus restricted
to one side. That side went through cell divisions and developed into a salamander; the other half simply degenerated.
Up until the 16-cell stage, if one nucleus escaped to the other
side of the constriction, twin salamanders could develop. Thus,
each of the nuclei of the blastula (at least up to the 16-cell stage)
was capable of directing and supporting development of the
whole organism.
But, as often happens in science, Spemann’s bisection experiments revealed a new phenomenon. Sometimes the half of
the blastula receiving an escaped nucleus did not develop.
When his loops bisected the gray crescent, both halves of the
zygote developed into a complete embryo. When he tied the
loops so the gray crescent was on only one side of the constriction, however, only that half of the zygote developed into a complete embryo (Figure 44.9). The half lacking gray crescent material underwent cell division, but even if it contained a nucleus,
it became a clump of undifferentiated cells that Spemann called
a “belly piece.” Spemann hypothesized that cytoplasmic factors
unequally distributed in the fertilized egg were necessary for
gastrulation and the development of a normal salamander.
To further test the hypothesis that cells receiving different
complements of cytoplasmic factors had different developmental fates, Spemann transplanted pieces of early gastrulas to various locations on other gastrulas. Guided by fate maps (see Figure 44.6), he was able to take a piece of ectoderm he knew
would develop into skin and transplant it to a region that normally becomes part of the nervous system, and vice versa.
When he performed these transplants in early gastrulas—
when the blastopore was just beginning to form—the transplanted pieces always developed into tissues that were appropriate for the location where they were placed. Transplanted
cells destined to become epidermis in their original location developed into nervous system tissue, and transplanted cells destined to become nervous system tissue in their original location
developed into host epidermis. Thus, Spemann learned that the
fates of the transplanted cells had not been determined before
the transplantation (see Figure 19.2).
In late gastrulas, however, the same experiment yielded opposite results. Transplanted cells destined to become epidermis
in their original location produced patches of skin cells in the host
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44.2
Gray crescent
bisected
|
HOW DOES GASTRULATION GENERATE MULTIPLE TISSUE LAYERS?
Gray crescent
isolated
931
INVESTIGATING LIFE
44.10 The Dorsal Lip Induces Embryonic Organization
1 Using a baby’s hair,
In a classic experiment, Hans Spemann and Hilde Mangold transplanted
the dorsal blastopore lip mesoderm of an early gastrula stage salamander
embryo. The results showed that the cells of this embryonic region, which
they dubbed “the organizer,” could direct the formation of an entire embryo.
Spemann constricted
a salamander zygote
along the plane of first
cleavage.
HYPOTHESIS Cytoplasmic factors in the early dorsal blastopore lip
2a This constriction bisects
organize cell differentiation in amphibian embryos.
the gray crescent.
2b This constriction
METHOD
restricts the gray
crescent to one half
of the zygote.
1. Excise a patch of mesoderm tissue from above the dorsal
blastopore lip of an early gastrula stage salamander embryo
(the donor).
2. Transplant the donor tissue onto a recipient embryo at the same
stage. The donor tissue is transplanted onto a region of
ectoderm that should become epidermis (skin).
Gray crescent
Blastocoel
3 Only those halves
Presumptive
mesoderm
with gray crescent
develop normally.
“Belly
piece”
Normal
Normal Normal
Dorsal
blastopore
lip
44.9 Gastrulation and the Gray Crescent Spemann’s
research revealed that gastrulation and subsequent normal
development in salamanders depends on cytoplasmic determinants localized in the gray crescent.
RESULTS
nervous system, and the transplanted cells from regions
that would develop into nervous system tissue produced neural tissue in the skin of the recipient. At some
point during gastrulation, the fates of the embryonic
cells had become determined.
Spemann’s next experiment, done with his student
Hilde Mangold, produced momentous results: they
transplanted the dorsal lip of the blastopore (Figure
44.10). When this small piece of tissue was transplanted
into the presumptive belly area of another gastrula, it
stimulated a second site of gastrulation—and a second complete embryo formed belly-to-belly with the
original embryo. Because the dorsal lip of the blastopore was apparently capable of inducing the host tissue to form an entire embryo, Spemann and Mangold
dubbed the dorsal lip tissue the primary embryonic organizer, or simply the organizer. For more than 80 years,
the organizer has been an active area of research.
yo u r B i oPort al.com
GO TO
Animated Tutorial 44.2 • Tissue Transplants
Reveal the Process of Determination
Transcription factors underlie the
organizer’s actions
Primary involution
(recipient of
dorsal lip)
C
Presumptive
epidermis
2 … and a second set of dorsal
Induced
nervous
system
neural structures forms in the
recipient embryo.
Mesoderm
Nervous
system
1 The donor tissue induces a
Endoderm
secondary involution…
3 Eventually a complete
secondary embryo forms,
attached to the original
embryo at the belly.
CONCLUSION
The cells of the dorsal blastopore lip can induce other
cells to change their developmental fates.
Go to yourBioPortal.com for original citations, discussions,
and relevant links for all INVESTIGATING LIFE figures.
With the advent of modern molecular methods, the
primary embryonic organizer has been studied intensively to discover the molecular mechanisms involved
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932
CHAPTER 44
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ANIMAL DEVELOPMENT
in its action. The distribution of the transcription factor β-catenin
in the late blastula corresponds to the location of the organizer
in the early gastrula, so β-catenin is a candidate for the initiator
of organizer activity. To prove that a protein is an inductive signal, it has to be shown that it is both necessary and sufficient for
the proposed effect. In other words, the effect should not occur if the candidate protein is not present (necessity), and the
candidate protein should be capable of inducing the effect
where it would otherwise not occur (sufficiency).
The criteria of necessity and sufficiency have been satisfied
for β-catenin. If β-catenin mRNA transcripts are depleted by injections of antisense RNA into the egg (see Section 18.4), gastrulation does not occur. If β-catenin is experimentally overexpressed in another region of the blastula, it can induce a second
axis of embryo formation, as the transplanted dorsal lip did in
the Spemann–Mangold experiments. Thus, β-catenin appears
to be both necessary and sufficient for the formation of the primary embryonic organizer—but it is only one component of a
complex signaling process.
How the presence of β-catenin creates the organizer, and how
the organizer then induces the beginnings of the body plan,
involves a complex series of interactions between transcription
factors and growth factors that control gene expression. What
follows is only a portion of this complex and still emerging story.
What you should take from this description is not the names of
the genes and gene products involved. Rather, we hope you will
gain a basic appreciation for how signaling molecules interact
to produce different combinations of signals that convey positional and temporal information. This information guides cells
into different paths of determination and differentiation.
Studies of early gastrulas revealed that primary embryonic organizer activity is generated by the interaction of β-catenin with
signals coming from the vegetal cells. Together, they activate
the expression of the transcription factor Goosecoid. Expression of the goosecoid gene depends on two signaling pathways.
The first of these pathways involves a goosecoid-promoting
transcription factor called Siamois. The siamois gene is normally
repressed by a ubiquitous transcription factor called Tcf-3, but
in cells in which β-catenin is present, an interaction between Tcf3 and β-catenin induces siamois expression (Figure 44.11). But
Siamois protein alone is not sufficient for goosecoid expression.
The second pathway involves mRNAs from the original egg
cytoplasm for a family of proteins called transforming growth
factor-β (TGF-β). TGF-β interacts with the Siamois protein to
control goosecoid transcription. Thus, you can see that it is a complex combination of factors that determines which cells become
the primary organizer.
The organizer changes its activity as it migrates
from the dorsal lip
Organizer cells begin the process of formation of the dorsal lip
of the blastopore. Specifically, these cells are at the center of
the dorsal lip and involute, moving forward on the midline (i.e.,
the middle of the anterior–posterior axis). The first organizer
cells to enter the embryo migrate anteriorly to become the head
endoderm and head mesoderm. Here, they induce neighboring
Gray crescent
1 Repression of siamois
by Tcf-3 proteins
prevents expression
of organizer-specific
genes.
2 b-Catenin in vegetal
cells below the gray
crescent blocks Tcf-3
repression of siamois
gene expression.
No b-catenin
Tcf-3 proteins siamois gene
repressed
DNA
b-catenin proteins
No transcription
siamois gene
activated
Transcription
Siamois protein
3 TGF-b-related signaling
pathway acts synergistically
with Siamois to activate the
goosecoid gene.
4 Goosecoid protein
goosecoid
Transcription
activates numerous
genes in the organizer.
44.11 Molecular Mechanisms of the Organizer In amphibians, the
organizing potential of the gray crescent depends on the activity of the
goosecoid gene, which in turn is activated by signaling pathways set up
in the vegetal cells below the gray crescent.
cells to participate in making structures of the head. Later organizer cells that involute into the embryo will induce structures of the trunk, and the last of the organizer cells to move inward from the dorsal lip will induce structures of the tail. How
does the nature of the organizer cells change to enable them to
induce head, trunk, or tail structures?
Inductive tissue interactions can suppress as well as activate.
As we learned above, the early organizer cells express the transcription factor Goosecoid, which activates genes encoding soluble signals. As these cells move forward in the blastocoel, they
come into contact with new populations of cells that produce
a number of different growth factors. For head structures to
form, certain of these growth factors have to be suppressed. The
anteriormost organizer cells, under the influence of Goosecoid,
produce and release antagonists to those growth factors.
The induction of trunk structures requires suppression of a
different set of growth factors. In organizer cells that involute
later than the head organizers, Goosecoid is no longer the dominant transcription factor, and these cells express different
growth factor antagonists. The induction of tail structures requires still different activities of the organizer cells that involute
last. Thus, the organizer cells express appropriate sets of growth
factor antagonists at the right times to achieve different patterns
of differentiation on the anterior–posterior axis.
The initiation of the development of the nervous system also
involves a suppressive tissue interaction. For a long time it was
thought that the involuting organizer cells actively induced the
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44.2
|
HOW DOES GASTRULATION GENERATE MULTIPLE TISSUE LAYERS?
INVESTIGATING LIFE
44.12 Differentiation Can Be Due to Inhibition of Transcription Factors
When organizer cells involute to underlie dorsal ectoderm along the embryo
midline, that overlying ectoderm becomes neural tissue rather than skin
(epidermis). But do the organizer cells cause dorsal ectoderm to become
neural tissue, or do they prevent this ectoderm from becoming skin?
HYPOTHESIS The default state of amphibian dorsal ectoderm is neural; it is
induced by underlying mesoderm to become epidermis.
METHOD
1. Excise the animal caps of late-stage frog blastulas and disperse
the cells in culture medium so there is no cell-to-cell contact. From
the culture, extract molecules of BMP4 (secreted by mesoderm
cells) and molecules of an inhibitor of BMP4.
Blastula
Dispersed
animal cap cells
in culture
Animal
cap
Gray crescent
2. Prepare four separate cultures of embryonic ectodermal cells. Incubate with
no additions (control); with BMP4 from step 1; with BMP4 inhibitor from
step 1; and with both molecules.
Control
Add BMP4
Add inhibitor
of BMP4
Add BMP4
+ inhibitor
Incubate
3. After incubation, extract mRNAs from the ectodermal cells and analyze for the
presence of mRNAs for marker proteins NCAM (neural cell adhesion molecule,
a neural protein) and/or keratin (an epidermal protein).
RESULTS
The control ectoderm (no inductive factors added) expresses the
neural marker. In the presence of mesodermal BMP4, ectoderm
expresses the epidermal marker. If BMP4 is inhibited, ectoderm
expresses the neural marker.
BMP4 BMP4 +
Control BMP4 inhibitor inhibitor
This control message is
from a gene expressed
in all cells and verifies
that each sample contains
similar amounts of mRNA.
Marker proteins
NCAM
Keratin
“Loading control”
CONCLUSION
The default state of amphibian dorsal ectoderm is neural.
BMP4 protein from mesoderm can induce ecotoderm cells to
differentiate into epidermis. Thus the organizer cells must
secrete an inhibitor of BMP4.
Go to yourBioPortal.com for original citations, discussions,
and relevant links for all INVESTIGATING LIFE figures.
933
overlying ectoderm to form neural tissue rather
than becoming epidermis. We now know, however, that epidermis is not the default state of
the dorsal ectoderm. Rather, the underlying
mesoderm secretes factors called BMP proteins
that induce the ectoderm to become epidermis.
The role of the involuting organizer cells is to
block that induction, allowing the overlying ectodermal cells to follow what is really their default pathway—differentiation into neural tissue (Figure 44.12).
Reptilian and avian gastrulation is an
adaptation to yolky eggs
The eggs of reptiles and birds contain a mass of
yolk, and the blastulas of these groups develop
as a disc of cells on top of the yolk (see Figure
44.3B). We will use the chicken egg to show
how gastrulation proceeds in a flat disc of cells
rather than in a ball of cells.
Cleavage in the chick results in a flat, circular layer of cells called a blastodisc (Figure
44.13). Between the blastodisc and the yolk
mass is a fluid-filled space. Some cells from the
blastodisc break free and move into this space.
These cells come together to form a continuous
layer called the hypoblast, which will later contribute to extraembryonic membranes that will
support and nourish the developing embryo.
The overlying cells make up the epiblast, from
which the embryo proper will form. Thus, the
avian blastula is a flattened structure consisting
of an upper epiblast and a lower hypoblast,
which are joined at the margins of the blastodisc. The blastocoel is the fluid-filled space
between the epiblast and hypoblast.
Gastrulation begins with a thickening in the
posterior region of the epiblast, caused by the
movement of cells toward the midline and then
forward along the midline (see Figure 44.13).
The result is a midline ridge called the primitive
streak. A depression called the primitive groove
forms along the length of the primitive streak.
The primitive groove functions as the blastopore, and cells migrate through it into the blastocoel to become endoderm and mesoderm.
In the chick embryo, no archenteron forms,
but the endoderm and mesoderm migrate forward to form the gut and other structures. At
the anterior end of the primitive groove is a
thickening called Hensen’s node, which in
birds, reptiles, and mammals is the equivalent
of the dorsal lip of the amphibian blastopore.
Many signaling molecules that have been identified in the frog organizer are also expressed
in Hensen’s node. Some cells that pass over
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CHAPTER 44
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ANIMAL DEVELOPMENT
44.13 Gastrulation in Birds Because their eggs contain a large yolk mass, bird and reptile
embryos have a flattened blastodisc and display a pattern of gastrulation very different from that of
amphibians.
Chick embryo viewed
from above
Flattened blastodisc
Yolk
4 …forming the primitive groove—
1 Posterior epiblast cells
change shape and thicken,
forming the primitive streak.
2 Cells migrate, converging
at the primitive streak and
causing it to elongate.
5 Cells generated in Hensen’s
the chick blastopore. Cells ingress
to the embryo interior through
Hensen’s node at the anterior end
of the groove.
3 The primitive
streak narrows
and lengthens…
node and passing into the
gastrula migrate anteriorly
and form head structures
and notochord.
Hensen’s
node
Anterior
Midline
Embryo
Yolk
Posterior
Primitive
streak
Hensen’s
node
Surface cells move
toward the groove and
into the gastrula.
Hensen’s node become the notochord and
organize the chick embryo in a manner similar to that of the frog embryo. And, as we
learned at the start of this chapter, the asymmetrical flow of extracellular fluid over this
node stimulates the primary cilia of nodal
cells, creating asymmetrical signaling cascades that determine the left–right asymmetry of the internal organs.
Primitive
groove
Hensen’s
node
Cells moving over
the sides of the
primitive groove
form mesoderm
and endoderm.
Epiblast
Endoderm
The hypoblast is
displaced by spreading
endoderm.
Blastocoel
Yolk
Hypoblast
Placental mammals retain the avian–
reptilian gastrulation pattern but lack yolk
Mammalian embryos (with the exception of monotremes) derive their nourishment from the maternal circulation, and therefore mammalian eggs do not have large amounts of yolk to constrain their patterns of cleavage and early development.
Nevertheless, mammals and birds evolved from reptilian ancestors, so it is not surprising that they share certain patterns of
early development. Earlier we described the development of
the mammalian inner cell mass (the equivalent of the avian epiblast) and the outer trophoblast.
As in avian development, in placental mammals the inner
cell mass splits into an upper layer called the epiblast and a
lower layer called the hypoblast. The embryo forms from the
epiblast, while the hypoblast contributes to the extraembryonic
membranes that will encase the developing embryo and help
form the placenta (see Figure 44.5). The epiblast also contributes
to the extraembryonic membranes; specifically, it splits off an
upper layer of cells that will form the amnion. The amnion will
grow to surround the developing embryo as a membranous sac
filled with amniotic fluid. Gastrulation occurs in the mammalian
epiblast just as it does in the avian epiblast. A primitive groove
forms, and epiblast cells migrate through the groove to become
layers of endoderm and mesoderm.
Primitive
groove
Cross section through chick embryo
44.2 RECAP
The cell movements of gastrulation convert the blastula into an embryo with three tissue layers. New
contacts between cells set up inductive signaling interactions that determine cell fates. Dorsal lip tissue
is the source of organizer cells that induce development of preliminary head, trunk, and tail structures.
•
Describe and compare the cell movements that occur
during gastrulation in a sea urchin, a frog, and a bird.
See Figures 44.7, 44.8, and 44.13
•
Explain the molecular basis for the inductive capabilities of the organizer. See pp. 931–932 and Figures
44.11 and 44.12
We have described how the fertilized egg develops into an embryo with three germ layers and how cellular signals trigger different patterns of differentiation. In the next section we will describe how organs and organ systems develop.
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© 2010 Sinauer Associates, Inc.
44.3
44.3
How Do Organs and Organ
Systems Develop?
Gastrulation produces an embryo with three germ layers that
are positioned to influence one another through inductive tissue interactions. During the next phase of development, called
organogenesis, many organs and organ systems develop simultaneously and in coordination with one another. An early
process of organogenesis in chordates that is directly related
to gastrulation is neurulation. Neurulation is the initiation of the
nervous system. We will examine neurulation in the amphibian embryo, but it occurs in a similar fashion in reptiles, birds,
and mammals.
|
HOW DO ORGANS AND ORGAN SYSTEMS DEVELOP?
935
Neural plate
(A)
(B)
Neural fold
Neural groove
Notochord
Ectoderm
Gut
Mesoderm
Endoderm
(C) Neural tube
The stage is set by the dorsal lip of the blastopore
Notochord
As we learned in the previous section, one group of cells that
passes over the dorsal lip of the blastopore moves anteriorly
and becomes the endodermal lining of the digestive tract. The
other group of cells that involutes over the dorsal lip becomes
chordamesoderm, so named because it forms a rod of mesoderm—the notochord—that extends down the center of the embryo. These cells also have important organizer functions (see
Figure 44.8). The notochord gives structural support to the developing embryo and is eventually replaced by the vertebral
column. The organizing capacity of the chordamesoderm enables the overlying ectoderm to become neural ectoderm (see
Figure 44.12). It does this by expressing signaling molecules (one
appropriately called Noggin and another one called Chordin)
that initiate differentiation of the different divisions of the nervous system.
Neurulation involves the formation of an internal neural tube
from an external sheet of cells. The first signs of neurulation are
flattening and thickening of the ectoderm overlying the notochord; this thickened area forms the neural plate (Figure 44.14A).
The edges of the neural plate that run in an anterior–posterior
direction continue to thicken to form ridges or folds. Between
these neural folds, a groove forms and deepens as the folds roll
over it to converge on the midline. The folds fuse, forming a
cylinder, the neural tube, and a continuous overlying layer of
epidermal ectoderm (Figure 44.14B–D).
Cells from the most lateral portions of the neural plate do not
become part of the neural tube, but disassociate from it and
come to lie between the neural tube and the overlying epidermis. These neural crest cells migrate outward to lead the development of the connections between the central nervous system
(brain and spinal cord) and the rest of the body.
The neural tube develops bulges at the anterior end, which
become the major divisions of the brain; the rest of the tube
becomes the spinal cord. In humans, failure of the neural folds
to fuse in this posterior region results in a birth defect known
as spina bifida. If the folds fail to fuse at the anterior end, an infant can develop without a forebrain—a condition called anencephaly. Although several genetic factors can cause these defects,
other factors are environmental, including maternal diet. The
incidence of neural tube defects in the United States in the early
1900s was as high as 1 in 300 live births; today it is less than 1
Coelom
Epidermis
Mesoderm
Neural tube
Neural
crest cells
Gut
(D)
Neural tube
Somite
Notochord
Epidermis
Coelom
44.14 Neurulation in a Vertebrate (A) At the start of neurulation, the
ectoderm of the neural plate (green) is flat. (B) The neural plate invaginates and folds, forming a tube. (C,D) The completely formed neural tube
seen in (C) diagrammatic form and (D) in a scanning electron micrograph
of a chick embryo.
in 1,000. A major factor in this improvement has been the inclusion of folic acid (a B vitamin, also known as folate) in the
mother’s diet. It is essential for pregnant women to ingest sufficient folic acid.
Body segmentation develops during neurulation
The vertebrate body plan, like that of arthropods, consists of repeating segments that are modified during development. These
segments are most evident as the repeating patterns of vertebrae, ribs, nerves, and muscles along the anterior–posterior axis.
As the neural tube forms, mesodermal tissues gather along
the sides of the notochord to form separate, segmented blocks
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936
CHAPTER 44
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ANIMAL DEVELOPMENT
(A)
(B)
Neural tube
Somites
2-Day chick embryo
Neural crest
Epidermis
Somites
Neural tube
Notochord
4-Day chick embryo
Neural crest cells
Neural tube
1 Repeating segments
of tissue–somites–
form from mesoderm
on either side of the
neural tube.
2 Each somite divides
into three layers of
cells. The upper will
contribute to skin…
muscles…
Migrating
mesenchyme
cells
Mesodermal
tissue (will
become somites)
3 …the middle to
Somite
forming
4 …and the lower
mesenchyme will
form cartilage of the
vertebrae and ribs.
7-Day chick embryo
5 Neural crest cells
migrate between the
layers and will
produce nerves and
other tissue.
of cells called somites (Figure 44.15). The somites produce cells
that will become the vertebrae, ribs, muscles of the trunk and
limbs, and the lower layer of the skin.
Nerves that connect the brain and spinal cord with tissues
and organs throughout the body are also arranged segmentally.
The somites help guide the organization of these peripheral
nerves, but the nerves are not of mesodermal origin. As we saw
above, when the neural tube fuses, the neural crest cells break
loose and migrate inward between the epidermis and the
somites and through the somites. These neural crest cells have
diverse fates, including the development of peripheral nerves.
As development progresses, the different segments of the
body change. Regions of the spinal cord differ, regions of the
vertebral column differ in that some vertebrae grow ribs of various sizes and others do not, forelegs arise in the anterior part
of the embryo, and hind legs arise in the posterior region.
Hox genes control development along the
anterior–posterior axis
How is mesoderm in the anterior part of a mouse embryo programmed to produce forelegs rather than hind legs? In Section
19.5, we saw how homeotic genes control body segmentation
in Drosophila. We also learned that all homeotic genes contain
a DNA sequence called the homeobox. Some of the genes directing gastrulation in the frog are homeobox genes—for example, goosecoid and siamois. In vertebrates, the homeotic genes
that control differentiation along the anterior–posterior body
axis are called Hox genes.
44.15 Developing Body Segmentation (A) Repeating blocks of tissue called somites form on either side of the neural tube. Muscle, cartilage, bone, and the lower layer of the skin form from the somites. (B) In
this SEM of somite formation in a chick embryo, the overlying ectoderm
has been removed and the neural tube and somites are seen from above.
In mammals, four Hox gene complexes reside on different
chromosomes in clusters of about 10 genes each. Remarkably,
the temporal and spatial expression of these genes follows the
same pattern as their linear order on their chromosome. That is,
the Hox genes closest to the 3′ end of each gene complex are expressed first and in the anterior of the embryo. The Hox genes
at the 5′ end of the gene complex are expressed later and in a
more posterior part of the embryo. As a result, different segments of the embryo receive different combinations of Hox gene
products, which serve as transcription factors (Figure 44.16; see
also Figure 20.2).
Whereas Hox genes give cells information about their position on the anterior–posterior body axis, other genes provide
information about their dorsal–ventral position. Tissues in each
segment of the body differentiate according to their dorsal–ventral location. The notochord provides many of these signals. One
example of a dorsal–ventral difference is seen in the spinal cord;
sensory nerve connections develop in the dorsal region, and
motor nerve connections in the ventral region. The protein Sonic
hedgehog (named for a video-game character), which is expressed in the mammalian notochord, induces cells in the overlying neural tube (i.e., the ventralmost cells of the neural tube)
to become motor neurons.
After the development of body segmentation, the formation
of organs and organ systems progresses rapidly. The development of an organ involves extensive inductive interactions of
the kind we saw in the example of the vertebrate eye (see Figure 19.10). These inductive interactions are a current focus of
study for developmental biologists.
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The genes closest to the 3′
end are expressed in the
anteriormost positions…
44.4
…and those closest to the 5′
end are expressed more
posteriorly.
b1 b2 b3 b4 b5 b6
b7 b8 b9
3′
5′
Hoxb
Expression
gradients from
anterior to
posterior of
embryo
For example, Hoxb1
is expressed in the
hindbrain…
…and Hoxb9
in the spinal
cord.
Hindbrain
Spinal co
rd
|
HOW IS THE GROWING EMBRYO SUSTAINED?
937
Extraembryonic membranes form with contributions
from all germ layers
The chicken provides a good example of how extraembryonic
membranes form from the germ layers created during gastrulation. In the chick, four membranes form—the yolk sac, the allantoic membrane, the amnion, and the chorion. The yolk sac is the
first to form, and it does so by extension of the hypoblast layer
along with some adjacent mesoderm. The yolk sac grows to enclose the entire body of yolk in the egg (Figure 44.17). It constricts at the top to create a tube that is continuous with the
gut of the embryo. However, yolk does not pass through this
tube. Yolk is digested by the cells of the yolk sac, and the nu-
Midbrain
Tho
racic
5-Day chick embryo
Lu
m
Forebrain
ba
r
Cervical
Embryo
(head end)
Mouse embryo
44.16 Hox Genes Control Body Segmentation Hox genes are
expressed along the anterior–posterior axis of the embryo in the same
order as their arrangement between the 3′ and 5′ ends of the gene complex. As a result of gene duplication during evolution, vertebrates have
four copies of the Hox gene complex shown.
Gut
Amnion
Amnionic
cavity
Chorion
Yolk
44.3 RECAP
Gastrulation sets up tissue interactions that initiate
organogenesis. Neurulation is initiated by organizer
mesoderm that forms the notochord.
•
Describe the formation of the neural tube in vertebrates. See p. 935 and Figure 44.14
•
How do somites relate to segmentation of the body
axis? See pp. 935–936 and Figure 44.15
•
Using information from this chapter and from Chapters 19 and 20, explain what Hox genes are and how
they instruct patterns of differentiation along the body
axis. See Figures 19.19, 20.1, and 44.16
The first extraembryonic
membrane is the yolk sac, which
is forming in the 5-day embryo.
The mesoderm and ectoderm
extend beyond the embryo to form
the chorion and the amnion.
9-Day chick embryo
Embryo
Gut
Amnion
Amnionic
cavity
Allantois
Chorion
You may be aware that in mammals the circulatory systems of
the fetus and mother are separate and that nourishment reaches
the fetus through the placenta and the umbilical cord. In the
next section we will examine the developmental events that result in the creation of the placenta.
44.4
How is the Growing Embryo
Sustained?
There is more to a developing reptile, bird, or mammal than the
embryo itself. As mentioned earlier, the embryos of these vertebrates are surrounded by several extraembryonic membranes,
which originate from the embryo but are not part of it. Extraembryonic membranes function in nutrition, gas exchange, and
waste removal. In mammals, they interact with tissues of the
mother to form the placenta.
Yolk
Allantoic
membrane
Yolk sac
The mesodermal and ectodermal
layers fuse below the yolk so that
the chorion lines the shell.
Mesodermal and endodermal
tissues form the allantois, a
sac for metabolic wastes.
44.17 The Extraembryonic Membranes In birds, reptiles, and mammals, the embryo constructs four extraembryonic membranes. The yolk
sac encloses the yolk, and the amnion and chorion enclose the embryo.
Fluids secreted by the amnion fill the amniotic cavity, providing an aqueous environment for the embryo. The chorion, along with the allantoic
membrane, mediates gas exchange between the embryo and its environment. The allantois stores the embryo’s waste products.
yo u r B i oPort al.com
GO TO
Web Activity 44.1 • Extraembryonic Membranes
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938
CHAPTER 44
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ANIMAL DEVELOPMENT
44.18 The Mammalian Placenta In humans
and most other mammals, nutrients and wastes
are exchanged between maternal and fetal
blood in the placenta, which forms from the
chorion and tissues of the uterine wall. The
embryo is attached to the placenta by the
umbilical cord. Embryonic blood vessels invade
the placental tissue to form fingerlike chorionic
villi. Maternal blood flows into the spaces surrounding the villi, and placental blood flows
through the villi so nutrients and respiratory
gases can be exchanged between the maternal
and fetal blood.
2 months
Fetus
Amnion
Chorion (fetal
portion of placenta)
Maternal portion
of placenta
Placenta
Uterus
Umbilical cord
Amnion
Umbilical arteries
(from fetus)
From fetus
To fetus
From fetus
trients are transported to the embryo through blood vessels that
form from mesoderm and line the outer surface of the yolk sac.
The allantoic membrane is also an outgrowth of the extraembryonic endoderm plus adjacent mesoderm. It forms the allantois, a sac for storage of metabolic wastes.
Ectoderm and mesoderm combine and extend beyond the
limits of the embryo to form the other extraembryonic membranes. Two layers of cells extend all along the inside of the
eggshell, both over the embryo and below the yolk sac. Where
they meet, they fuse, forming two membranes, the inner amnion and the outer chorion. The amnion surrounds the embryo,
forming the amniotic cavity. The amnion secretes fluid into
the cavity, providing a protective environment for the embryo.
The outer membrane, the chorion, forms a continuous membrane just under the eggshell (see Figure 44.17). It limits water
loss from the egg and also works with the enlarged allantoic
membrane to exchange respiratory gases between the embryo
and the outside world.
Extraembryonic membranes in mammals form
the placenta
In placental mammals, the first extraembryonic membrane to
form is the trophoblast, which is already apparent by the fifth
cell division (see Figure 44.4). When the blastocyst reaches the
uterus and hatches from its encapsulating zona pellucida, the
trophoblast cells interact directly with the endometrium. Adhesion molecules expressed on the surfaces of these cells attach
them to the uterine wall. By secreting proteolytic enzymes, the
trophoblast burrows into the endometrium, beginning the
process of implantation (see Figure 44.5). Eventually, the entire trophoblast is within the wall of the uterus. The trophoblast
cells then send out numerous projections, or villi, to increase the
surface area of contact with maternal blood.
Meanwhile, the hypoblast cells proliferate to form what in
the bird would be the yolk sac. But there is no yolk in eggs of
placental mammals, so the yolk sac contributes mesodermal tissues that interact with trophoblast tissues to form the chorion.
The chorion, along with tissues of the uterine wall, produces
the placenta, the organ that exchanges nutrients, respiratory
Umbilical vein
(to fetus)
Chorionic
villus
Maternal vein
(to mother)
Maternal artery
(from mother)
gases, and metabolic wastes between the mother and the embryo (Figure 44.18).
At the same time the yolk sac is forming from the hypoblast,
the epiblast produces the amnion, which grows to enclose the entire embryo in a fluid-filled amniotic cavity. The rupturing of the
amnion and chorion and the loss of the amniotic fluid (a process
called “water breaking”) herald the onset of labor in humans.
An allantois also develops in mammals, but its importance
depends on how well nitrogenous wastes can be transferred
across the placenta. In humans the allantois is minor; in pigs it
is important. In humans and other mammals, allantoic tissues
contribute to the formation of the umbilical cord, by which the
embryo is attached to the chorionic placenta. It is through the
blood vessels of the umbilical cord that nutrients and oxygen
from the mother reach the developing fetus, and wastes, including carbon dioxide and urea, are removed (see Figure 44.18).
44.4 RECAP
The extraembryonic membranes of reptiles, birds,
and mammals sustain the growing embryo. In reptiles
and birds, these membranes surround the embryo
within the shelled egg. In mammals the extraembryonic membranes form the placenta, an organ that exchanges nutrients, respiratory gases, and metabolic
wastes between the mother and the embryo.
•
Describe each of the four extraembryonic membranes
and their functions in the developing chick egg. See
pp. 937–938 and Figure 44.17
•
Explain the role of the trophoblast in the early development of a mammalian embryo. See p. 938
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44.5
44.5
What Are the Stages of
Human Development?
In humans, gestation, or pregnancy, lasts about 266 days, or 9
months. In smaller mammals gestation is shorter—for example,
21 days in mice—and in larger mammals it is longer—for example, 330 days in horses and 600 days in elephants. The events
of human gestation can be divided into three periods of roughly
3 months each, called trimesters.
|
WHAT ARE THE STAGES OF HUMAN DEVELOPMENT?
939
diation, drugs, chemicals, and pathogens that can cause birth
defects. An embryo can be damaged before the mother even
knows she is pregnant. A classic and tragic case is that of
thalidomide, a drug widely prescribed in Europe in the late
1950s to treat nausea. Women who took this drug in the fourth
and fifth weeks of pregnancy, when the embryo’s limbs are beginning to form, gave birth to children with missing or severely
malformed arms and legs.
Organ development begins in the first trimester
Organ systems grow and mature during the second and
third trimesters
Implantation of the human blastocyst begins about 6 days after
fertilization. After implantation, gastrulation occurs, tissues differentiate, the placenta forms, and organs begin to develop. The
heart begins to beat during week 4, and limbs are formed by
week 8 (Figure 44.19 A,B). By the end of the first trimester, most
organs have started to form. The embryo is about 8 centimeters
long and weighs about 40 grams (less than 2 ounces); it would
fit neatly in a teaspoon. At about this point in time, the human
embryo is medically and legally referred to as a fetus. (This distinction is not made for other mammals; developing mice, for
example, remain embryos until they are born.)
The first trimester is a time of rapid cell division and tissue
differentiation. Signal transduction cascades and the resulting branching sequences of developmental processes are in
their early stages. Therefore, the first trimester is the period
during which the embryo is most sensitive to damage from ra-
During the second trimester the fetus grows rapidly to a weight
of about 600 grams. The limbs of the fetus elongate, and the fingers, toes, and facial features become well formed (Figure
44.19C). Eyebrows and fingernails grow and the fetus’s nervous system develops rapidly. Fetal movements are first felt by
the mother early in the second trimester, and they become progressively stronger and more coordinated.
The fetus grows rapidly during the third trimester (Figure
44.19D). As the trimester approaches its end, internal organs
mature. The digestive system begins to function, the liver stores
glycogen, the kidneys produce urine, and the brain undergoes
cycles of sleep and waking. A human infant is born as soon as
the last of its critical organs—the lungs—mature.
Although the first-trimester embryo is the most susceptible
to adverse effects of drugs, chemicals, and diseases, the potential for serious effects from exposure to environmental factors
(A) 4 weeks
(C) 4 months
Actual length ~0.4 cm (4 mm)
Actual length ~10 cm
(B) 8 weeks
(D) 9 months
Actual length ~3 cm
Actual length ~40 cm
44.19 Stages of Human
Development (A) At 4 weeks of
gestation, most of the embryo’s organ
systems have been formed and the
heart is beating. (B) The body structures of this 8-week-old embryo are
forming rapidly, and it is visibly a male.
The umbilical cord attaches the
embryo to the placenta (upper left).
(C) At 4 months, the fetus has fully
formed limbs with fingers and toes,
and moves freely within the amniotic
cavity. (D) This fetus is well along in its
ninth month. Soon its lungs will be
mature enough to trigger the onset of
contractions and birth.
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CHAPTER 44
940
|
ANIMAL DEVELOPMENT
exists throughout pregnancy and continues after birth. Severe
protein malnutrition, alcohol, and cigarette smoke are examples
of factors that can cause low birth weight, mental retardation,
and other developmental complications.
Developmental changes continue throughout life
Development does not end with birth. Obviously, growth continues until adult size is reached, and even when growth stops,
organs of the body continue to repair and renew themselves
through cycles of cell replacement by the progeny of undifferentiated stem cells. In humans especially, enormous developmental changes occur in the brain in the years between birth
and adolescence. Especially in the early years, there is a great
deal of plasticity in the organization of the nervous system as
the connections between neurons develop.
For example, a child born with misaligned eyes (a condition known as strabismus) will use mostly one eye. The connections to the brain from that eye will become strong while
connections from the other eye remain weak, and the child will
develop with reduced visual acuity and depth perception. If eye
alignment is corrected in the first 3 years of life, the connections
between the eyes and the brain can improve and the child is
likely to develop normal vision. After the age of 3, correcting
the connections between the eyes and the brain is less likely to
result in improvement, and visual impairments may persist.
Thus plasticity in human visual system development declines
during early childhood. However, recent data indicate that it is
not lost entirely and may be reactivated even in adulthood.
44.5 RECAP
Human gestation lasts 9 months and can be divided
into 3 trimesters. At the end of the first trimester, the
fetus is very small but most of its organs have begun
to form. In the second trimester, limbs elongate and
the fetus moves. By the end of the third trimester,
most organs have begun to function.
•
Why is a first-trimester embryo particular sensitive to
environmental risks? See p. 939
CHAPTER SUMMARY
44.1
•
•
How Does Fertilization Activate Development?
The sperm and the egg contribute differentially to the zygote.
The sperm contributes a haploid nucleus and, in most species, a
centriole. The egg contributes a haploid nucleus, nutrients, ribosomes, mitochondria, mRNAs, and proteins.
In amphibians, the cytoplasmic contents of the egg are not distributed homogeneously, and they are rearranged after fertilization to set up the major axes of the future embryo. The nutrient
molecules are generally found in the vegetal hemisphere,
whereas the nucleus is found in the animal hemisphere.
44.2
•
Cleavage is a period of rapid cell division. Except in mammals,
little if any gene expression occurs during cleavage. Cleavage
can be complete or incomplete, and the pattern of cell divisions
depends on the orientation of the mitotic spindles. The result of
cleavage is a ball or mass of cells called a blastula. Review
•
Early cell divisions in mammals are unique in being slow and
allowing for gene expression early in the process. These cell
divisions produce a blastocyst composed of an inner cell mass
that becomes the embryo and an outer cell mass that becomes
the trophoblast. At the time of implantation, the trophoblast
secretes molecules that help the blastocyst implant in the uterine wall. Review Figures 44.4 and 44.5
A fate map can be created by labeling specific blastomeres and
observing what tissues and organs are formed by their progeny.
Review Figure 44.6
•
Some species undergo mosaic development, in which the fate of
each cell is determined during early divisions. Other species,
including vertebrates, undergo regulative development, in which
remaining cells can compensate for cells lost in early cleavages.
The initial step of sea urchin and amphibian gastrulation is
inward movement of certain blastomeres. The site of inward
movement becomes the blastopore. Cells that move into the
blastula become the endoderm and mesoderm; cells remaining
on the outside become the ectoderm. Cytoplasmic factors in
the vegetal pole cells are essential to initiate development.
Review Figures 44.7 and 44.8
•
The dorsal lip of the amphibian blastopore is a critical site for
cell determination. It has been called the primary embryonic
organizer because it induces determination in cells that pass
over it during gastrulation. Review Figures 44.8, 44.9, and
•
The protein β-catenin activates a signaling cascade that induces
the primary embryonic organizer and sets up the anterior–posterior body axis. Review Figures 44.2, and 44.11
Gastrulation in reptiles and birds differs from that in sea urchins
and frogs because the large amount of yolk in reptile and bird
eggs causes the blastula to form a flattened disc of cells.
Figure 44.3
•
Gastrulation involves massive cell movements that produce
three germ layers and place cells from various regions of the
blastula into new associations with one another. Review Figure
44.7, ANIMATED TUTORIAL 44.1
•
Review Figures 44.1 and 44.2
•
How Does Gastrulation Generate Multiple Tissue
Layers?
44.10, ANIMATED TUTORIAL 44.2
•
Review Figure 44.13
•
Although their eggs have no yolk, placental mammals have a
pattern of gastrulation similar to that of reptiles and birds.
44.3
•
How Do Organs and Organ Systems Develop?
Gastrulation is followed by organogenesis, the process whereby tissues interact to form organs and organ systems.
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CHAPTER SUMMARY
•
•
•
In the formation of the vertebrate nervous system, one group of
cells that migrates over the blastopore lip is determined to
become the notochord. The notochord organizes the overlying
ectoderm to thicken, form parallel ridges, and fold in on itself to
form a neural tube below the epidermal ectoderm. The nervous
system develops from this neural tube. Review Figure 44.14
The notochord and neural crest cells participate in the segmental organization of mesoderm into structures called somites
along the body axis. Rudimentary organs and organ systems
form during these stages. Review Figure 44.15
In vertebrates, Hox genes determine the pattern of
anterior–posterior differentiation along the body axis in mammals. Other genes, such as sonic hedgehog, contribute to dorsal–ventral differentiation. Review Figure 44.16
44.4
•
•
How is the Growing Embryo Sustained?
The embryos of reptiles, birds, and mammals are protected and
nurtured by four extraembryonic membranes. In birds and rep-
tiles, the yolk sac surrounds the yolk and provides nutrients to
the embryo, the chorion lines the eggshell and participates in
gas exchange, the amnion surrounds the embryo and encloses
it in an aqueous environment, and the allantois stores metabolic wastes. Review Figure 44.17, WEB ACTIVITY 44.1
In mammals, the chorion and the trophoblast cells interact with
the maternal uterus to form a placenta, which provides the
embryo with nutrients and gas exchange. The amnion encloses
the embryo in an aqueous environment. Review Figure 44.18
44.5
•
•
941
What Are the Stages of Human Development?
Human pregnancy, or gestation, can be divided into three
trimesters. The embryo forms in the first trimester; during this
time, it is most vulnerable to environmental factors that can
lead to birth defects. During the second and third trimesters the
fetus grows, the limbs elongate, and the organ systems mature.
Development continues throughout childhood and throughout
life.
SELF-QUIZ
1. Fertilization involves all of the following except
a. equal contributions of cell organelles from sperm and egg.
b. joining of sperm and egg haploid nuclei.
c. induction of rearrangements of the egg cytoplasm.
d. sperm binding to specific sites on the egg surface.
e. metabolic activation of the egg.
2. Which of the following does not occur during cleavage in
frogs?
a. A high rate of mitosis
b. Reduction in the size of cells
c. Expression of genes critical for blastula formation
d. Orientation of cleavage planes at right angles
e. Unequal division of cytoplasmic determinants
3. How does cleavage in mammals differ from cleavage in
frogs?
a. Slower rate of cell division
b. Formation of tight junctions
c. Expression of the embryo’s genome
d. Early separation of cells that will not contribute to the
embryo
e. All of the above
4. Which statement about gastrulation is true?
a. In frogs, gastrulation begins in the vegetal hemisphere.
b. In sea urchins, gastrulation produces the notochord.
c. In birds, cells from the surface of the blastodisc move
down through the primitive groove to form the hypoblast.
d. In mammals, gastrulation occurs in the hypoblast.
e. In sea urchins, gastrulation produces only two germ layers.
5. Which of the following was a conclusion from the experiments of Spemann and Mangold?
a. Cytoplasmic determinants of development are homogeneously distributed in the amphibian zygote.
b. In the late blastula, certain regions of cells are determined
to form skin or nervous tissue.
c. The dorsal lip of the blastopore can be isolated and will
form a complete embryo.
d. The dorsal lip of the blastopore can initiate gastrulation.
e. The dorsal lip of the blastopore gives rise to the neural
tube.
6. Which of the following is true of human development?
a. Most organs begin to form during the second trimester.
b. Gastrulation takes place in the oviducts.
c. Genetic diseases can be detected by sampling cells from
the chorion.
d. Implantation occurs through interactions of the zona
pellucida with the uterine lining.
e. Exposure to drugs and chemicals is most likely to cause
birth defects when it occurs in the third trimester.
7. Which of the following characterizes neurulation?
a. The notochord forms a neural tube.
b. The neural tube is formed from ectoderm.
c. A neural tube forms around the notochord.
d. The neural tube forms somites.
e. In birds, the neural tube forms from the primitive groove.
8. Which statement about trophoblast cells is true?
a. They are capable of producing monozygotic twins.
b. They are derived from the hypoblast of the blastocyst.
c. They are endodermal cells.
d. They secrete proteolytic enzymes.
e. They prevent the zona pellucida from attaching to the
oviduct.
9. Which of the following is part of the embryonic contribution to placenta formation?
a. Amnion
b. Chorion
c. Ectoderm
d. Allantois
e. Zona pellucida
10. When is the developing human most susceptible to the
occurrence of birth defects from radiation or chemical
insults?
a. At the time of birth
b. During the third trimester
c. During the first trimester
d. When it is a zygote
e. During the final stages of organ formation
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942
CHAPTER 44
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ANIMAL DEVELOPMENT
FOR DISCUSSION
1. If you found a protein that was localized to a small group
of cells in the frog blastula, how would you determine
whether that protein played a role in development?
Address the issues of sufficiency and necessity.
2. During gastrulation in birds, the sonic hedgehog gene is
expressed only on the left side of Hensen’s node. What
might be the cause of this expression pattern, and what is
its significance?
3. Much of the early work of describing animal development
was done on sea urchins, amphibians, and chickens. Most of
the recent work on the molecular mechanisms of animal
development has been done on nematodes, fruit flies,
zebrafish, and mice. Why do you think there has been a shift
in the animal models used by developmental biologists?
4. If all the mitochondria and mitochondrial DNA in the
embryo come from the egg, what implications does this
have for using mitochondrial DNA for molecular evolutionary studies?
5. There is currently much controversy over therapeutic
cloning as a way of obtaining embryonic stem cells to treat
diseases. Given that human development is regulative—in
other words, twinning can occur if an early blastocyst is
divided into two cell masses—can you think of a way to
guarantee a source of isogenic (i.e., identically matching a
person’s own body) stem cells for an individual without
resorting to therapeutic cloning? Assume isolated cells can
be preserved indefinitely in a frozen state.
A D D I T I O N A L I N V E S T I G AT I O N
It is hypothesized that the differential development of the different body segments is due to the differential expression of
Hox genes along the anterior–posterior body axis. For example,
in mammals, ribs develop in anterior body trunk segments but
not in posterior segments. Using the mouse as a model, how
would you test this hypothesis?
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