Overview: A Body-Building Plan for Animals
It takes only about 9 months for a single-celled zygote to be transfigured into a newborn
human, built of trillions of differentiated cells organized into specialized tissues and organs.
Tail
Brain
Pharyngeal
Pouches
Heart
6 to 8 week human embryo
Limb bud
1 mm
Vertebrae
Preformation 2000 yrs. earlier, Aristotle proposed
“homunculus”
epigenesis – form emerges gradually
1694
Development is determined by the
genome of the zygote & differences
that arise between early embryonic
cells that set the stage for the
expression of different genes.
In some species, this is due to the
uneven distribution of cytoplasmic
determinants in the unfertilized
egg. These affect development of
the cells that inherit them during
mitosis. In other species, this is
due to their location in different
embryonic regions. In most, it’s
a combination. Selectively
controlled gene expression leads to
cell differentiation (specialization).
The timely communication of
instructions during morphogenesis
occurs by cell signaling among
embryonic cells, so differentiated
cells end up in the appropriate
locations.
47.1: After fertilization, embryonic development proceeds through cleavage, gatrulation, & organogenesis
1 Contact – The sperm contacts the egg’s jelly coat, triggering exocytosis from the sperm’s acrosome.
2 Acrosomal reaction – Hydrolytic enzymes make a hole in the jelly coat, while actin filaments form the acrosomal
process. This protrudes from the sperm head and penetrates the jelly coat, binding receptors in the egg membrane
that extend through the vitelline layer.
3 Fusion – A hole is made in the vitelline layer, allowing contact and fusion of the gamete membranes.
The membrane becomes depolarized, resulting in the fast block to polyspermy.
5 Cortical reaction – Fusion of the membranes triggers an increase of Ca2+ in the egg’s cytosol, causing cortical
granules to fuse with the plasma membrane. This leads to swelling of the perivitelline space, hardening of the
vitelline layer, and clipping of sperm binding receptors. The fertilization envelope is the slow block to polyspermy.
One function of
fertilization is
egg activation.
Acrosomal
reaction
Sperm plasma
membrane
Contact and fusion
of sperm and egg
Entry of sperm
membranes
4 nucleus
Cortical reaction
Contact
Basal body
(centriole)
Sperm
head
Sperm
nucleus
Actin
Acrosome
Jelly coat
Sperm-binding
receptors
Acrosomal
process
Na+ Na+ Na+
+
Fused plasma Na
Na+
Cortical membranes 2+
+
Ca
Ca2+Na Na+
granule Ca2+
Ca2+Na+
Hydrolytic enzymes Perivitelline
2+
Ca
space
+
2+ Cortical granule Na
Vitelline layer
Ca
2+
Ca
membrane
Ca2+Na+
Egg plasma
EGG CYTOPLASM Ca2+
2+
2+
membrane
Ca2+
Ca
Ca
Fertilization
envelope
Na+
500 µm
More About The Cortical Reaction
1 sec before
fertilization
10 sec after
fertilization
Point of
sperm
entry
20 sec
30 sec
Spreading wave
of calcium ions
Sperm binding appears to activate an IP3-DAG signal transduction pathway that causes Ca2+ to be
released from ER beginning at the site of sperm entry and propagating in a wave across the egg.
Within seconds, the high [Ca2+] induces fusion of cortical granules that release mucopolysacharides,
producing an osmotic gradient, drawing water into the perivitelline space, separating the vitelline layer.
Cortical granule enzymes: 1) degrade proteins that hold the vitelline layer to the plasma membrane,
2) clip off sperm receptor proteins and 3) harden the vitelline layer into the fertilization envelope.
Although studied in detail in sea urchins, this is known to occur in vertebrates, including mammals.
Activation of the Egg
Ca2+,
Seconds
Increased [Ca2+] also induces
increased pH, cellular respiration
& protein synthesis (activated).
Sperm cells do not contribute
any materials. Eggs can be
first cell division occurs.
Minutes
activated by injection of
& temperature shock,
(parthenogenesis), even with the
egg nucleus removed! Proteins
& mRNAs in the egg cytoplasm
are sufficient for activation.
The sperm nucleus begins to swell
and merges with the egg nucleus
forming the diploid zygote.
DNA synthesis begins and the
In other species the timing
differs partly because the eggs
are arrested at a specific stage
of meiosis (humans = metaphase II).
Upon fertilization, meiosis is
quickly completed.
1
Binding of sperm to egg
2
3
4
Acrosomal reaction & fusion: plasma membrane
depolarization (fast block to polyspermy)
6
8
10
20
30
40
50
1
Increased intracellular calcium level
Cortical reaction begins (slow block to polyspermy)
Formation of fertilization envelope complete
2
Increased intracellular pH (MINE = not in mouse!)
3
4
5
Increased cellular respiration & protein synthesis
10
20
30
40
60
90
Fusion of egg and sperm nuclei complete
Onset of DNA synthesis
First cell division
Fertilization in Mammals
In terrestrial animals, fertilization is internal. Female reproductive tract secretions “activate” sperm
by altering molecules on the surface and increasing motility. Human sperm requires ~6 hrs exposure.
Nuclei do not fuse immediately. Their envelopes disperse and the chroms. come together after mitosis.
(12-36 hrs.)
1 Sperm migrates through follicle cells and binds to receptors (not shown) in the zona pellucida.
2 Acrosomal reaction – Hydrolytic enzymes make a hole in the zona pellucida.
3 Breakdown of the zona pellucida allows the sperm to reach the egg plasma membrane.
Sperm membrane proteins bind receptors on the egg membrane and they fuse.
4 The sperm nucleus and other components enter the egg. (basal body becomes centrosome - duplicates)
5 Cortical reaction – Cortical granule enzymes harden the zona pellucida, which blocks polyspermy. (no fast block)
Follicle
cell
4
3
2
1
Zona
pellucida
Egg plasma
membrane
Acrosomal
vesicle
5
Sperm
Cortical
basal
granules
body Sperm
nucleus
EGG CYTOPLASM
Establishing The Axes
Polarity of the egg determines the anterior-posterior axis before
fertilization. The animal hemisphere is deep gray due to melanin
granules in the cortex. The absence of melanin in the
vegetal hemisphere allows the yellow yolk to be visible.
The animal membrane and associated cortex rotate toward the point
Animal
hemisphere
Animal pole
Point of
sperm entry
Vegetal
hemisphere
of sperm entry. The vegetal cortex rotates toward the animal hemisphere.
This allows molecules in the vegetal cortex to interact with cytoplasmic
Vegetal pole
molecules in the animal hemisphere, forming cytoplasmic determinants
that initiate development of dorsal structures.
Cortical rotation establishes the dorsal-ventral axis and also exposes the
gray crescent, a marker for the dorsal side that is covered by animal cortex
prior to rotation. The first cleavage bisects the gray crescent.
Point of
sperm
entry
Gray
crescent
Anterior
Once anterior-posterior and dorsal-ventral are defined,
Right
so is the left-right axis.
Future
dorsal
side
Dorsal
Ventral
Left
First
cleavage
Posterior
Cleavage
Blastomeres
Blastocoel
fertilization
envelope
Zygote
Four-cell stage
Morula
Blastula
During cleavage, cells undergo S and M cell cycle stages, but virtually skip the G1 and G2 stages.
This results in no protein synthesis and the embryo does not enlarge. The cytoplasm is partitioned
into blastomeres. The first 5-7 divisions form a cluster, known as the morula within which the fluidfilled blastocoel begins to form and is completed in the blastula, a hollow ball of cells. Different regions
of cytoplasm with different cytoplasmic determinants end up in separate blastomeres. Uneven
distribution of mRNAs, proteins and yolk determine the egg and zygote’s polarity. (NOT IN MAMMALS)
The planes of division follow a specific pattern relative to the poles. Yolk is most concentrated toward
the vegetal pole and decreases toward the animal pole (also where polar bodies are budded from
during oogenesis).
Cleavage
In the frog, the first two divisions are meridional
(vertical), resulting in four blastomeres of equal size
extending from the animal pole to the vegetal pole.
The third, is equatorial (horizontal). However, the
uneven distribution of yolk in the zygote, displaces
the mitotic apparatus so that the four blastomeres
in the animal hemisphere are smaller. The effect
of the yolk persists, so that the blastocoel is located
in the animal hemisphere.
Zygote
0.25 mm
2-cell
stage
forming
4-cell
stage
forming
Other animals have less yolk, but still have an
animal-vegetal axis due to uneven distribution of
other substances. The blastomeres are more likely
to be of similar size and the blastocoel centrally
8-cell
located, but the general cleavage pattern seen in
stage
frogs is seen in all deuterostomes.
Animal pole
Blastula
(cross
section)
Eight-cell stage (viewed
from the animal pole)
0.25 mm
Blastocoel
Vegetal pole
Blastula (at least 128 cells)
Cleavage
Disk of
cytoplasm
Yolk
Fertilized egg
In birds, what we call the yolk is actually the
egg cell with a very small disk of cytoplasm
at the animal pole. This enormous cell is surrounded
by a protein-rich solution (white) that also provides nutrients.
Cleavage is restricted to the yolk-free cytoplasm
(meroblastic cleavage vs. holoblastic cleavage). This produces
Zygote
Four-cell stage
(just the disk)
cap of cells called the blastoderm which sort into upper (epiblast)
and lower (hypoblast) layers. The cavity between is the blastocoel
and this embryonic stage is the avian equivalent of the blastula.
In insects, the zygote’s nucleus is within a mass of yolk.
Cleavage begins with the nucleus undergoing mitotic divisions
without cytokinesis. Several hundred nuclei spread throughout
the yolk, then migrate to the outer edge of the embryo.
Membrane forms around each, forming the blastula,
which consists of a single layer of about 6,000 cells
surrounding a mass of yolk.
Blastoderm
Cutaway view of
the blastoderm
Blastocoel
BLASTULA
YOLK MASS
Epiblast
Hypoblast
Gastrulation (Sea Urchin)
VIDEO CLIP
The morphogenetic process called gastrulation is a dramatic
Future ectoderm
rearrangement of the blastula to form a 3-layered embryo
Future mesoderm Germ Layers
Future endoderm
(gastrula) with a primitive gut. Gastrulation is driven by
Animal
pole
the same general mechanisms in all species: changes in
Blastocoel
cell motility, shape and adhesion. The three layers
Mesenchyme
produced, are embryonic germ layers that will eventually cells
develop into all the tissues and organs of the adult animal. Vegetal
Vegetal
Key
plate
Gastrulation begins at the vegetal pole where cells detach
and enter the blastocoel as migratory mesenchyme cells.
Cells near the vegetal pole flatten into a vegetal plate that
buckles inward through invagination forming the endodermlined archenteron. Mesenchyme cells send out filopodia from
the archenteron tip that contract and drag the archenteron
across the blastocoel.
The open end of the archenteron, which will become the anus,
is called the blastopore. When the other end touches the
ectoderm, the two layers fuse, forming the mouth, completing
the primitive digestive tube (gut).
pole
Blastocoel
Filopodia
pulling
archenteron
tip
Archenteron
Mesenchyme
cells
Blastopore
50 µm
Ectoderm
Mouth
Some of the mesenchyme cells (mesoderm) will eventually
secrete calcium carbonate to form a simple internal skeleton. Mesenchume
The gastrula develops into a ciliated larva that drifts as
plankton until it metemorphoses into the adult benthic
animal.
Blastocoel
(mesoderm
forms future
skeleton)
Archenteron
Blastopore
Digestive tube (endoderm)
Anus (from blastopore)
GASTRULA
Gastrulation (Frog)
Gastrulation is more complicated in the frog:
1) yolk-laden cells of the vegetal hemisphere
2) blastula wall more than one cell thick.
Gastrulation begins on the dorsal side along
the gray crescent and produces the dorsal lip
of the blastopore. Invagination continues to be
initiated until the two ends of the blastopore
meet on the ventral side forming a complete
circle. All along the blastopore, future
mesoderm and endoderm cells roll over the
edge of the lip into the interior (involution).
CROSS SECTION
SURFACE VIEW
Animal pole
Blastocoel
Dorsal
lip of
blastopore
Dorsal lip
of blastopore
Vegetal pole
BLASTULA
Blastocoel
shrinking
Archenteron
Involution
The blastocoel collapses during this process,
displaced by the archenteron cavity and the
blastopore encercles a yolk plug.
As is the sea urchin, the frog is a deuterostome.
Blastocoel
remnant
VIDEO CLIP
Ectoderm
Mesoderm
Endoderm
Key
Future ectoderm
Future mesoderm
Future endoderm
Yolk plug
Yolk plug
GASTRULA
Gastrulation (Chick)
BLASTODERM
Epiblast
Primitive
streak
Future
ectoderm
Endoderm
Migrating
cells
(mesoderm)
Hypoblast
YOLK
All the cells that will form the embryo come from the epiblast. Cells move toward the midline of the
blastoderm, then detach and move inward through the primitive streak. Some move down to become
endoderm, some laterally into the blastocoel to form mesoderm and remaining epiblast cells
become ectoderm. Hypoblast cells later segregate from the endoderm and form portions of the yolk
sac and a stalk connecting the yolk mass to the embryo.
Organogenesis (Frog)
Organogenesis involves more localized
morphogenic changes in tissue. Folds,
splits and dense clustering (condensation)
begin organ formation. The notochord
Neural folds
Neural
fold
is formed from dorsal mesoderm that
condenses just above the archenteron.
Neural plate
Outer layer
of ectoderm
Signals from the notochord cause the
LM
1 mm
Neural Neural
fold
plate
Notochord
Ectoderm
Mesoderm
Endoderm
Archenteron
Neural plate formation
ectoderm above it to form the neural
Neural tube
plate, which curves inward, rolling itself
Neural crest
into the neural tube.
The neural crest develops where the tube
pinches off from the ectoderm. These
cells migrate to various parts of the embryo,
forming peripheral nerves, teeth, skull
Neural crest
bones, and many other types of cells.
Fourth germ layer??
Formation of the neural tube
Organogenesis (Frog)
Somites
Eye
SEM
Neural tube
Tail bud
1 mm
Notochord
Neural
crest
Coelom
Somite
Somites are condensations that occur in strips of mesoderm lateral to the
notochord. Some dissociate into mesenchymal cells. The notochord
functions as a core around which somites gather and form vertebrae.
Parts of the notochord persist as the inner portion of vertebral disks.
Somite cells also form the muscles of the axial skeleton. Lateral to the
somites, the mesoderm splits into two layers that form the lining of the
coelom.
In the chick, the borders of the blastoderm fold downward and come
together, pinching the embryo into a three-layered tube joined to the
yolk. Other events occur much as they do in the frog. Rudiments of
most major organs have formed by 56 yours.
Organogenesis (Chick)
Eye
Neural tube
Notochord
Archenteron
(digestive cavity)
Somites
Forebrain
Somite
Coelom
Endoderm
Mesoderm
Ectoderm
Archenteron
Lateral fold
Heart
Blood
vessels
Somites
Yolk stalk
Form extraembryonic
Yolk sac
membranes
Neural tube
YOLK
Early organogenesis
Late organogenesis
Adult derivatives of the three embryonic germ layers in vertebrates.
Developmental Adaptations of Amniotes
(dehydration & shock) Amnion
Amniotic
cavity
with
amniotic
fluid
(metabolic waste disposal &
gas exchange with chorion)
Allantois
Albumen
(nutrients, dehydration
& shock)
Embryo
Yolk
Shell
(semipermeable)
(nutrients)
Chorion
(gas exchange)
Yolk sac (blood vessels transport
yolk nutrients)
Vertebrate embryos require an aqueous envirnonment. Two effective structures have evolved to
enable this on land: 1) The shelled egg, and 2) the uterus. In both, embryos are surrounded by fluid
within a sac formed by the amniotic membrane, or amnion. Reptiles, birds & mammals are amniotes.
Germ layers outside the embryo develop into four extraembryonic membranes that provide life
support for the embryo. NOTE: Each membrane forms from two germ layers.
Mammalian Development
Uterus
-Fertilization and the earliest stages of
development are in the oviduct.
-Eggs are small, store little nutrients,
and have not been shown to be polar.
-Cleavage is holoblastic, however,
gastrulation and early organogenesis
Blastocyst
is similar to birds and reptiles.
arrives
-Early cleavage is slow (human: 1st @ 36 hrs.,
2nd @ 60 hrs., 3rd @ 72 hrs.)
-Blastomeres are equal size and tightly
adhere, so the embryo appears smooth.
Maternal
blood
vessel
1 At the completion of cleavage, the
embryo has over 100 cells (blastocyst)
around a central cavity (blastocoel). At one end,
is the inner cell mass, which develops
Blastocyst
into the embryo and extraembryonic
implants.
membranes.
Endometrium
(uterine lining)
Inner cell mass
Trophoblast
Blastocoel
Expanding
region of
trophoblast
Epiblast
Hypoblast
Trophoblast
2 The trophoblast (epithelium) secretes enzymes that break down the endometrium (implantation).
The trophoblast thickens and extends projections into the maternal tissue, eroding capillaries,
so that blood bathes trophoblastic tissues. The inner cell mass forms a flat disk with an epiblast
and a hypoblast. As in birds, the human embryo develops almost entirely from epiblast cells.
Mammalian Development
3 Epiblast cells move inward through a primitive
streak to form mesoderm and endoderm.
Amnion
At the same time, extraembryonic membranes
begin to form. The invading trophoblast,
mesodermal cells derived from the epiblast,
and adjacent endometrial tissue all contribute
to the formation of the placenta.
4 The three layered embryo is now surrounded
by proliferating extraembryonic mesoderm
and the four extraembryonic membranes:
The chorion completely surrounds the
embryo and other membranes and functions
in gas exchange. The amnion eventually
encloses the embryo in a fluid filled cavity.
The yolk sac encloses another fuid filled cavity
and is the site of early blood cell formation.
The allantois is incorporated into the umbilical
cord and forms blood vessels to exchange
gasses, nutrients and waste with the placenta.
Gastrulation is followed by the organogenesis
of the notochord, neural tube, and somites.
Expanding
region of
trophoblast
Amniotic
cavity
Epiblast
Hypoblast
Chorion (from
Trophoblast)
Yolk sac (from
hypoblast)
Extraembryonic
membranes start Extraembryonic mesoderm cells
(from epiblast)
to form and
gastrulation
begins.
Allantois
Amnion
Chorion
Ectoderm
Mesoderm
Endoderm
Yolk sac (no yolk!)
Gastrulation has produced a
three-layered embryo with four
extraembryonic membranes.
Extraembryonic
mesoderm
By the end of the first trimester, rudiments of all the major organs have developed.