Brad Martinsen, Ph.D.
Department of Pediatrics
Pediatric Cardiology
Program in Human Anatomy
Human Embryology
Week 1: Fertilization to Implantation
Week 2: The Bilaminar Embryo
Week 3: The Trilaminar Embryo
Neurulation and Neural Crest
Musculoskeletal System
Head & Neck
Ear and Eye Development
Heart
Gastrointestinal Development
Renal System
Reproductive System
http://cna.uc.edu/embryology/
Welcome to the Dental Human Embryology Course (DENT 5315/OBIO-8024)
Brad Martinsen, Ph.D. (marti198@umn.edu)
Lecture 1:
Topic
Assigned Reading
Week 1: Fertilization to Implantation
pages 18-22
Week 2: The Bilaminar Embryo
pages 38-44
Week 3: The Trilaminar Embryo
pages 53-60
Neurulation and Neural Crest
pages 64-65, 86-93
Musculoskeletal System
pages 60-64, 7987, 315-328
The PowerPoint notes pages give a complete review of the reading
assignments (Larson’s Human Embryology, 3rd ed.) and what I will say in
lecture. You can also refer to the Larson’s Human Embryology Website
(http://cna.uc.edu/embryology/) and click on contents for Animations,
Updates, Self-tests, and Glossaries of Terms for each Chapter.
*Use reading assignments to clarify anything said in lecture or in the notes.
Not all detail in the reading assignments will be on the exams.
1
Fertilization
Fertilization and first days of development.
A. Fertilization (occurs in the ampulla of the uterine tube):
1. Sperm binding occurs through the interaction of sperm glycosyltransferases and the ZP3
receptors located on the Zona Pellucida
2. The fusion of the spermatozoon cell membrane (aided by acrosomal enzymesacrosin)
with the oocyte membrane causes the mechanism (cortical reaction) that prevents polyspermy,
as well as causing the oocyte to resume meiosis (Fig 1-10). The sperm mitochondria and tail
degenerate.
3. The secondary oocyte completes the second meiotic metaphase and anaphase producing
another polar body. The first polar body simultaneously completes its second meiotic division.
The oocyte is now considered to be a definitive oocyte.
4. The female and male pronuclei fuse, forming the diploid and 2N nucleus of the fertilized
zygote. This is the zero time point of embryonic development (Fig 1-10C). Ploidy refers to
the number of copies of each chromosome present in the nucleus. N number refers to the
number of copies of each unique double-stranded DNA molecule in the nucleus.
2
First Days of Development
Day 0-5
Compaction
starts
First days of development.
As the zygote travels down the oviduct it undergoes cleavage without increasing its size. This
subdivides the large zygote into many smaller daughter cells called blastomeres.
24 Hours:
First cleavage (Fig 1-11 and 1-12)
48 Hours:
Second cleavage
3 Days:
Embryo consists of 6 to 12 cells, reorganization (compaction: Uvomorulin,
a glycoprotein found on the surface of blastomeres, is involved in
compaction) of the blastomeres, starts at the 8 cell stage. The centrally
placed blastomeres are now called the inner cell mass (they give rise to most
of the embryo proper, which is also called the embryoblast). The
blastomeres at the periphery constitute the outer cell mass, they are the
primary source for the membranes of the placenta. It is also refered to as the
trophoblast.
4 Days:
Embryo consists of 16 to 32 cells called morula.
5 Days:
The embryo is now called a blastocyst. A large cavity called the blastocyst
cavity forms due to the hydrostatic pressure. The embryoblast cells form a
compact mass at one side of the cavity (embryonic pole), while the
trophoblast is organized into a thin, single-layered epithelium (Fig 1-11).
6 Days:
Blastocyst implants into the uterine wall (Fig 1-13). The blastocyst hatches
from the zona pellucida before implanting. The trophoblast at the embryonic
pole differentiates to produce the syncytiotrophoblast, and begins to implant
the blastocyst into the uterine endometrium.
Some of the proliferating trophoblast cells lose their membranes and form a
syncytium. The trophoblast cells, which form the wall of the blastocyst,
retain their cell membranes and constitute the cytotrophoblast (Fig 2-1).
3
First Days of Development
Day 6
Ectopic pregnancy results when a blastocyst implants in the peritoneal cavity
on the surface of the ovary, within the oviduct, or at an abnormal site in the
uterus. Because the blood vessels at abnormal implantation sites are apt to
rupture, ectopic pregnancy is often revealed by symptoms of abdominal pain
and/or vaginal bleeding.
4
First Days of Development Day 7
Day 7
The embryoblast consists of an external layer called the epiblast (primary
ectoderm) and an internal layer called the hypoblast (primary endoderm). The
resulting two-layered embryoblast is called the bilaminar germ disc (Fig 2-2).
5
Week Two (Day 8)
Day 8
As implantation progresses, the expanding syncytiotrophoblast gradually
envelops the blastocyst (Fig 2-3).
A layer of epiblast cells is gradually displaced toward the embryonic pole by
accumulating fluid. These cells differentiate into amnioblasts, which form the
amniotic membrane. The newly formed cavity is called the amniotic cavity
(Fig 2-3).
6
Day 9
Day 9
A layer of epiblast cells is gradually displaced toward the embryonic pole by
accumulating fluid. These cells differentiate into amnioblasts, which form the
amniotic membrane. The newly formed cavity is called the amniotic cavity
(Fig 2-3).
Cells at the periphery of the hypoblast begin to migrate out over the inner
surface of the cytotrophoblast. Eventually, these migrating hypoblast cells
completely line the former blastocyst cavity.
7
Day 10
Day 10
This new membrane is now called the exocoelomic membrane or Heuser’s
membrane (Fig 2-4).
The former blastocyst cavity is now called the primary yolk sac or
exocoelomic cavity (Fig 2-4).
Once the primary yolk sac is formed, a thick, loosely reticular layer of cellular
material called the extraembryonic reticulum is secreted between Heuser’s
membrane and the cytotrophoblast.
8
Day 11
Day 11
Extraembryonic mesoderm cells that arise from the epiblast at the caudal end
of the bilaminar germ disc begin to migrate out. Two layers result--one
coating the outer surface of Heuser’s membrane and the other lining the inner
surface of the cytotrophoblast (Fig 2-4B).
9
Day 12
Day 12
The growth and migration of the extraembryonic mesoderm gradually
separates the amnion from the cytotrophoblast.
On day 12, a second wave of proliferation in the hypoblast produces a new
membrane that migrates out over the inside of the extraembryonic mesoderm,
pushing the primary yolk sac in front of it. This new layer becomes the
endodermal lining of the definitive (secondary) yolk sac (Fig 2-5A-C).
10
Days 12-13
Chorion membrane
consists of?
Days 12-13
On day 12, a second wave of proliferation in the hypoblast produces a new
membrane that migrates out over the inside of the extraembryonic mesoderm,
pushing the primary yolk sac in front of it. This new layer becomes the
endodermal lining of the definitive (secondary) yolk sac (Fig 2-5A-C).
As the definitive yolk sac develops on day 13 the primary yolk sac breaks up
into disintegrating exocoelomic vesicles (Fig 2-5C and Fig 2-6).
11
Day 13
Day 13
As the definitive yolk sac develops on day 13 the primary yolk sac breaks up
into disintegrating exocoelomic vesicles (Fig 2-5C and Fig 2-6).
12
Days 14-15
Primary ectoderm:
primordial germ cells,
endothelial cells, and
hematopoietic stem cells.
Extraembryonic mesoderm
of the yolk sac wall is a
major site of hematopoiesis.
Chorion membrane
consists of?
Days 14-15
By 14-15 days the bilaminar germ disc has formed and is suspended in the
chorionic cavity by a thick connecting stalk.
The extraembryonic mesoderm forming the outer layer of the yolk sac wall is a
major site of hematopoiesis. Cells from the primary ectoderm migrate into the
yolk sac forming the first endothelial cells and hematopoietic stem cells. The
coordinated development of these cells into the vitelline vasculature is called
blood island formation.
Meckel’s diverticulum: The yolk sac normally disappears before birth, but if it
persists a digestive tract anomaly may develop.
13
Origin of the germ line
Migration of the primordial germ cells into
posterior body wall.
2 Weeks
->ovarian follicle cells
4-6 weeks
10th
Thoracic
Vertebrae
->Sertoli cells
Teratoma:
Origin of the germ line.
Migration of the primordial germ cells: Cells that give rise to the gametes originate within the
primary ectoderm during the second week of development. They then detach from the
ectoderm and migrate into the yolk sac (Timeline, pg2). At first they are seen as a mass of
extraembryonic mesoderm at the caudal end of the embryo and then within the endoderm of
the yolk sac. These cells are called the primordial germ cells, and their lineage constitutes the
germ line (Fig. 1-1A). During the fourth week, the primordial germ cells migrate into the
posterior body wall of the embryo from the yolk sac (Fig 1-1B). The primordial germ cells
continue to multiply by mitosis during their migration. In the dorsal body wall, these cells
come to rest on either side of the midline in the loose mesenchymal tissue adjacent to the tenth
thoracic vertebrae level that will form the gonads. The germ cells then induce the adjacent
coelonic epithelium and mesonephros to proliferate and form the primitive sex cords. This
creates a swelling (genital ridges/primordial gonads) medial to each mesonephros on either
side of the vertebrae column.
Teratoma: stray germ cells can get stranded along the route of migration at inappropriate sites
in the dorsal body wall. These cells can eventually give rise to a tumor.
14
Week Three--Gastrulation
Gastrulation.
Primitive Streak: Between days 15 and 16 the primitive streak forms. It starts
out as a faint groove at the caudal end of the bilaminar germ disc. Eventually
it deepens forming a primitive groove with a depression (primitive pit) at the
cranial end. The mound of epiblast cells surrounding the pit is called the
primitive node (Fig 3-1). The fundamental cranial/caudal, left/right, and
ventral/dorsal axes are established at this time.
15
Week Three--Gastrulation
Gastrulation continues.
Formation of definitive endoderm and intraembryonic mesoderm:
On day 16, epiblast cells near the primitive streak proliferates and migrates
through the primitive streak into the space between the epiblast and hypoblast.
Some of the cells displace the entire hypoblast forming a new layer called the
definitive endoderm. It gives rise to the lining of the future gut and gut
derivatives (Fig 3-2). Other epiblast cells diverge into the space between the
epiblast and the nascent definitive endoderm to form a third layer, the
intraembryonic mesoderm(Fig 3-2).
16
Week Three--Gastrulation
Gastrulation continues.
Other epiblast cells diverge into the space between the epiblast and the nascent
definitive endoderm to form a third layer, the intraembryonic mesoderm(Fig 32).
17
Week Three--Gastrulation
Gastrulation continues.
Mesoderm cells that ingress through the primitive node migrate cranially to
form the prechordal plate and notochordal process(Fig 3-3).
Mesoderm cells that ingress through the primitive groove migrate to form the
mesoderm lying on either side of the midline (Fig 3-6 and Fig 3-7). The
epiblast at this point takes on a new name, the ectoderm. Thus all three layers
of the trilaminar germ disc (the ectoderm, mesoderm and definitive endoderm)
were formed from the epiblast.
The buccopharyngeal membrane breaks down eventually to form the opening
to the oral cavity, while the cloacal membrane disintegrates to form the
openings of the anus and the urinary and genital tracks.
18
Week Three--Gastrulation
Gastrulation continues.
The notochordal process is initially formed as a hollow mesodermal process
and then transformed into a solid notochord between days 16 and 22 (Fig 37). During the transformation period the notochord process fuses with the
endoderm. This allows the yolk sac cavity to transiently communicate with the
amniotic cavity through an opening at the primitive pit called the neurenteric
canal. During the transformation process, some cells of endodermal origin
may become incorporated into the notochord.
19
Neurulation
Induction of the neural plate.
The axial mesoderm (prechordal and notochordal plate) induces the overlying
ectoderm to form the neural plate (Fig 4-8). Formation of the neural tube
begins on day 22 at the level of the first five somites (Fig 4-9). Closure of the
cranial neuropore is bidirectional, and final closure occurs in the area of the
future forebrain. Closure of the caudal neuropore is craniocaudal and finishes
at the level of the second sacral segment (the level of somite 31).
20
Neural Crest
Neural Crest.
During neurulation neural crest cells begin to migrate in a craniocaudal wave
(beginning on day 22). Cephalic neural crest cells detach and migrate before
closure of the cranial neural tube. In contrast, trunk neural crest cells detach as
the lateral lips of the neural tube fuse (Fig 4-13). Neural crest cells are an
extremely important population of cells that migrate into the embryo to form a
variety of structures (Fig 4-12 & 4-14).
21
Neural Crest
Cranial
Vagal
Trunk
Lumbosacral
Neural Crest.
During neurulation neural crest cells begin to migrate in a craniocaudal wave
(beginning on day 22). Cephalic neural crest cells detach and migrate before
closure of the cranial neural tube. In contrast, trunk neural crest cells detach as
the lateral lips of the neural tube fuse (Fig 4-13). Neural crest cells are an
extremely important population of cells that migrate into the embryo to form a
variety of structures (Fig 4-12 & 4-14).
22
Clinical Applications
-->Neural crest cells that give rise to Odontoblasts stop
migrating and settle down against the buccal epithelium
at locations of the future teeth.
--> Teeth are composite structures made up of the
outer white enamal which covers the teeth above the gums
and the inner dentin, a different mineralized tissue forming
the root and interior of the teeth.
--> Dentin and enamel are extracellular products of two
different types of cells, the ameloblasts (enamel) and
odontoblasts (dentin).
Odontoblasts arise from the neural crest. Neural crest cells that give rise to
Odontoblasts stop migrating and settle down against the buccal epithelium at
locations of the future teeth. Teeth are composite structures made up of the
outer white enamal which covers the teeth above the gums and the inner
dentine, a different mineralized tissue forming the root and interior of the teeth.
Dentine and enamel are extracellular products of two different types of cells,
the ameloblasts (enamel) and odontoblasts (dentine).
23
Clinical Applications
Rieger Syndrome:
-->Embryological disturbance of the neural crest ectoderm
results in severe enamel hypoplasia, conical and misshapen
teeth, hypodontia, hyperdonita, and impactions. Abnormalities
of migration along the buccal epithelium results in ectopism.
Rieger Syndrome: Embryological disturbance of the neural crest ectoderm
results in severe enamel hypoplasia, conical and misshapen teeth, hypodontia,
hyperdonita, and impactions. Abnormalities of migration along the buccal
epithelium results in ectopism.
24
Paraxial, intermediate, and lateral plate mesoderm
Axial skel.
Vol muscl.
Dermis
Splanchnopleuric
Somatopleuric
mesoderm
Urinary system
Genital system
Paraxial, intermediate, and lateral plate mesoderm.
As the primitive streak regresses, the mesoderm cells that migrated laterally
begin to form cylindrical structures called the paraxial, intermediate and lateral
plate mesoderm on either side of the notochord (Fig 3-8).
The paraxial mesoderm gives rise to Somitomers (Fig 3-9) which then develop
into somites (Fig 3-10, 3-11, and 3-12). The somites then give rise to the axial
skeleton, voluntary musculature and part of the dermis.The fist 7 somitomeres
do not go on to form somites. Instead, they give rise to the muscles of the face,
jaw, and throat.
Intermediate Mesoderm
Fig 3-12).
urinary system and genital system (Fig 3-10 and
Lateral Plate Mesoderm splits into the splanchnopleuric mesoderm (sometimes
refered to as intraembryonic visceral mesoderm and becomes the mesothelial
covering of the visceral organs) and somatopleuric mesoderm (sometimes
refered to as intraembryonic somatic mesoderm and it gives rise to the lining
of the body wall, parts of the limbs, and dermis) (Fig 3-8).
25
Form ~44 pairs of somites then
caudal most 7 somites disapear
giving rise to 37 pairs.
1-4 somites: occipital part of the
skull, bones of nose and eyes, &
muscles of the tongue.
Next 8 pairs: form in the
presumptive cervical region. Give
rise to occipital bone and cervical
vertebrae, and assoc. muscles.
Next 12 pairs: Thoracic somites-->
thoracic vertebrae, and associated
muscles.
5 lumbar somites, 5 sacral somites,
&
Finally 3 coccygeal somites.
The embryo initially forms ~44 pairs of somites, but eventually the caudal
most 7 somites disappear giving rise to 37 pairs.
1-4 somites: occipital part of the skull, bones of nose and eyes, & muscles of
the tongue.
Next 8 pairs: form in the presumptive cervical region. Give rise to occipital
bone and cervical vertebrae, and assoc. muscles.
Next 12 pairs: Thoracic somites-->
thoracic vertebrae, and associated muscles.
5 lumbar somites, 5 sacral somites, & Finally 3 coccygeal somites.
26
Somites subdivide into three kinds
of mesodermal primordium.
Dermatome
Myotome
Day 22
Day 28
Day 31
Role of somites in the formation of the vertebrae and musculature of the
developing embryo.
Somites subdivide into three kinds of mesodermal primordium (Fig 4-1 and 4
6):
1. Dermatomes: form the dermis of the scalp, neck and trunk.
2. Myotomes: form the segmental musculature of the back and the
anterolateral body wall.
3. Sclerotomes: surround the notochord and neural tube and eventually form
the vertebral bodies and vertebral arches and also contribute to the base of
the skull. The costal processes that appear on the vertebral bodies in the
thoracic region go on to form the ribs.
27
Vertebral Column
5-7 weeks
Adult >25yrs
Vertebral Column.
Mesodermal cells from the sclerotome migrate and condense around the
notochord to form the centrum, around the neural tube to form the vertebral
arches, and in the body wall to form the costal processes .
Centrum forms the vertebral body.
Vertebral arches form the pedicles, laminae, spinous process, articular
processes, and the transverse processes.
Costal processes form the ribs.
28
Vertebral Column
Intersegmental position of the vertebrae
How do the spinal nerves escape from the developing vertebral canal?
Why do 8 cervical sclerotomes produce 7 cervical vertebrae?
Intersegmental position of the vertebrae (Fig 4-2, and Fig 4-3):
As mesodermal cells from the sclerotome migrate towards the notochord and
neural tube, they split into a cranial portion and a caudal portion. The caudal
portion of each sclerotome fuses with the cranial portion of the succeeding
sclerotome, which results in the intersegmental position of the verebra. The
splitting of the sclerotome is important because if allows the developing spinal
nerve a route of access to the myotome that it must innervate.
29
Vertebral Column
Intervertebral disk: Consists
of the:
nucleus pulposus (remnant of
the notochord) and
annulus fibrosus (outer rim
of fibro-cartilage, derived
from mesoderm/sclerotome).
Secondary cartilaginous joints (symphyses) (Fig 4-4) are the joints between the
vertebral bodies in which the intervertebral disks play a role.
An intervertebral disk consists of a Nucleus pulposus and an Annulus
fibrosus. The Nucleus pulposus is a remnant of the embryonic notochord.
By 20 years of age, all notochordal cells have degenerated such that all
notochordal vestiges in the adult are limited to just a noncellular matrix. The
Annulus fibrosus is an outer rim of fibrocartilage derived from mesoderm
found between the vertebral bodies.
30
Skeletal Muscle
Trunk musculature
Back Muscles
Intercostal &
Abdominal muscles
Trunk musculature.
Trunk musculature is derived from myotomes in the trunk region that partition
into dorsal epimeres and ventral hypomeres (Fig 4-6).
Epimeres develop into the intrinsic back muscles (erector spinae).
Hypomeres develop into the prevertebral, intercostal, and abdominal muscles.
31
Limb Skeleton and Musculature
development
Somites induce somatopleuric plate to form the limb buds.
Day 24: the upper limb bud appears in the
lower cervical region.
Day 28: the lower limb bud appears in the
lower lumbar region.
AER
Limb Skeleton and Musculature Development.
Somites induce the formation of limb buds in the somatopleuric lateral plate mesoderm.
24 days: the upper limb bud appears in the lower cervical region (Fig 11-1A&B).
28 days: the lower limb bud appears in the lower lumbar region.
Apical ectodermal ridge induces the differentiation of the limb buds (Fig 11-1C&D). The
late-formed mesenchyme at the tip of the limb bud differentiates into the distal segments of the
limb (Fig 11-2). The early-formed mesenchyme at the base of the bud differentiates into the
proximal segments of the limb (Fig 11-2).
Differentiation of the limb bud occurs during the 5th to 8th weeks of development (Fig 11-3).
The upper limbs develop in advance of the lower limbs, but by the end of limb development
the two limbs are nearly synchronized.
32
Somite, lateral plate mesoderm, and
neural crest contribution to the limb
Bone, tendons, ligaments
Somites->musculature of the limb
N.C. forms the
Melanocytes & Schwann
Cells.
Somite, lateral plate mesoderm, and neural crest contribution to the limb.
The lateral plate mesoderm gives rise to the bones, tendons, ligaments, and
vasculature of the limbs.
The somitic mesoderm that migrates into the developing limb gives rise to the
musculature (Fig 11-5).
The neural Crest Cells that migrate into the limb give rise to melanocytes and
Schwann cells.
Note: The quail-chick chimera system was used to study the cell populations
that give rise to the various elements of the limbs.
33
Limb Musculature development
Cervical and thoracic somite cells invade the
upper limb bud to form the limb
musclulature.
Lumbar somite cells invade the lower limb
buds to form the leg musculature.
Dorsal (Posterior) Muscle Mass:
Upper limb-->extensors and supinators
Lower limb-->extensors and abductors
Ventral (Anterior) Muscle Mass:
Upper limb-->flexors and pronators
Lower limb-->flexors and adductors
Limb musculature development.
During the fifth week, somitic mesoderm invades the limb bud and forms two
large condensations, one dorsal to the axial mesenchymal column and one
ventral to it (Fig 11-7). The cells of the condensations differentiate into
myoblasts (muscle cell precursors).
The dorsal muscle mass gives rise to the extensors and supinators of the
UPPER limb and to the extensors and abductors of the LOWER limb.
The ventral muscle mass gives rise to the flexors and pronators of the
UPPER limb and to the flexors and adductors of the LOWER limb. Note:
Some muscles migrate from their site of origin and acquire different functions.
34
Rotation of the limbs
Note that the upper limbs rotate laterally 90 degrees, whereas the
lower limbs rotate medially 90 degrees, which sets up the following
anatomic situations:
1.
Flexor compartment of the upper limb is anterior, whereas the
flexor compartment of lower limb is posterior.
2.
Extensor compartment of upper limb is posterior, whereas the
extensor compartment of lower limb is anterior.
Rotation of the limbs (Fig. 11-10).
The upper limbs appear in week 4 as small bulges oriented in a coronal plane. They undergo
a horizontal flexion in week 6 so that they are now oriented in a parasagittal plane. They
rotate laterally 90 degrees during weeks 6 to 8 so that the elbow points posteriorly, the
extensor compartment lies posterior, and the flexor compartment lies anterior. The 90 degree
lateral rotation of the upper limb bud causes the originally straight segmental pattern of
innervation to twist into a spiral in the adult.
The Lower limbs appear in week 4 (about 4 days after the upper limb bud) as small bulges
oriented in a coronal plane. They undergo horizontal flexion in week 6 so that they are now
oriented in a parasagittal plane. They rotate medially 90 degrees during weeks 6 to 8 so that
the knee points anteriorly, the extensor compartment lies anteriorly, and the flexor
compartment lies posterior. The rotation causes the originally straight segmental pattern of
innervation to become twisted in a spiral in the adult.
Final anatomic situation of the limbs: Note that the upper limbs rotate laterally 90
degrees, whereas the lower limbs rotate medially 90 degrees. This sets up the following
anatomic situations:
Flexior compartment of the upper limb is anterior, whereas the flexor compartment of the
lower limb is posterior.
Extensor compartment of the upper limb is posterior, whereas the extensor compartment of the
lower limb is anterior.
35