L.12.L13 EMBRYOLOGY 2. FIRST 4 WEEKS.pdf

KILIMANJARO CHRISTIAN MMEDICAL UNIVERSITY COLLEGE
Faculty of Nursing and Rehabilitation Medicine
Department of Anatomy and Neuroscience
EMBRYOLOGY LECTURE (L12, L13)
FISRT FOUR WEEKS OF EMBRYONIC DEVELOPMENT
Date: November 25th 2022, from 1:30 Pm, GYM.
Lecturer: J. S. Kauki, BSc, MSc, on PhD, Email: jskauki@gmail.com.
Office ext. 69 IPH Block, 3RD Floor, Anatomy dept.
S12. S13. Embryology lect.BSc.1 1

Objectives
After the session, students should be able to describe;
• Major events that occur during the first week of development;
• Major events that occur in the Second week of development;
• Major events that occur in the 3rd week of development
• Major events that occur in the 4th week of development
S14 Embryology lect.BSc.1 2

Introduction: 1st week
• Human development begins at fertilization when a sperm fuses with an oocyte to form a
single cell, the zygote.
• Zygote is a highly specialized, totipotent cell i.e. capable of giving rise to any cell type
• This zygote develops into a fully formed human in a period of 09 months in the uterus
• Major events which occur in the 1st week of development include:
 Fertilization
 Cleavage
 Formation of blastocyst
 Implantation

1st week: Fertilization
• The usual site of fertilization is in the ampulla of the uterine tube (Fallopian tubes)
• If the oocyte is not fertilized, it slowly passes along the tube to the body of uterus,
where it degenerates and is resorbed.
• Fertilization may occur in other parts of the tube, but does not occur in body of the
uterus
• Chemical signals secreted by oocyte and surrounding follicular cells attract capacitated
sperms to the oocyte
• Carbohydrate-binding molecules and gamete-specific proteins on the surface of sperms
are involved in sperm–egg recognition and union

1st week: Fertilization
• Fertilization is a complex sequence of coordinated molecular events that begins with contact
between a sperm and an oocyte and ends with the intermingling of maternal and paternal
chromosomes at metaphase of the 1st mitotic division of the zygote, a unicellular embryo
• It takes approximately 24 hours
• Defects at any stage in the sequence of these events may cause death of the zygote
• Events of fertilization:
 Passage of a sperm through the corona radiata
 Penetration of the zona pellucida
 Fusion of cell membranes of the oocyte and sperm
 Formation of the male pronucleus
 Fusion of male and female pronuclei

1st week: Events of fertilization
• Passage of a sperm through the corona radiata
 Hyaluronidase released from the acrosome of the sperm and tubal mucosal enzymes
disperse follicular cells of the corona radiata.
 Movements of tail of the sperm aid its penetration of the corona radiata
• Penetration of the zona pellucida
 The enzymes esterase, acrosin, and
neuraminidase from acrosome appear to cause
lysis of the zona pellucida, thereby forming a
path for the sperm to enter the oocyte.
 The most important of these enzymes is acrosin,
a proteolytic enzyme.

• Fusion of cell membranes of the oocyte and
sperm
 The cell membranes of the oocyte and
sperm fuse and break down at the area of
fusion
 The head and tail of the sperm enter the
cytoplasm of the oocyte but the sperm’s cell
membrane and mitochondria remain behind

• As soon as spermatozoan enters oocyte, the egg responds in 3 ways:
1. Cortical and zona reactions
2. Resumption of the 2nd meiotic division
3. Metabolic activation of the egg

Cortical and zona reactions:
• Cortical granules are secretory vesicles filled with lysosomal enzymes poised at the cortex of a
secondary oocyte.
• Upon stimulation by sperm contact at fertilization, they secrete their contents (Cortical reaction)
• As a result of the release of cortical oocyte granules, which contain lysosomal enzymes:
 Oocyte membrane becomes impenetrable to other spermatozoa
 Zona pellucida alters its structure and composition to prevent sperm binding and penetration
(Zona reaction)
• These reactions prevent polyspermy (penetration of more than one spermatozoan into the
oocyte) S14 Embryology lect.BSc.1 9

1st week: Events of Fertilization
Completion of 2nd meiotic division
• Oocyte completes its 2nd meiotic division immediately after
entry of the spermatozoan
• One of the daughter cells, which receives hardly any
cytoplasm, becomes 2nd polar body; the other daughter cell is
the definitive oocyte
• Following decondensation of the maternal chromosomes,
nucleus of the mature oocyte becomes the female pronucleus
Metabolic activation of the egg
• Concentration of Ca2+ in the cytosol increases
• Activation encompasses the initial cellular and molecular events associated with early
embryogenesis

• Formation of the male pronucleus
 Within the cytoplasm of the oocyte, spermatozoan moves forward until it lies
close to the female pronucleus.
 Its nucleus becomes swollen and forms the male pronucleus
 The tail detaches and degenerates
• During growth of the pronuclei, they replicate their
DNA i.e. each chromosome splits into 2
chromatids
• The oocyte containing the two haploid pronuclei is
called an ootid
• Morphologically, the male and female pronuclei
are indistinguishable
Ootid

Events of fertilization
• Fusion of male and female pronuclei
 Male and female pronuclei come into close contact and lose their nuclear envelopes
 Chromosomes organize on the spindle in preparation for a normal mitotic division
 As the pronuclei fuse into a single diploid aggregation of chromosomes, the ootid becomes
a zygote
 The zygote is genetically unique because half of its chromosomes came from the mother
and half from the father
 This mechanism forms the basis of biparental inheritance and variation of the human
species (together with crossing over of chromosomes during meiosis)

Effect of Fertilization
• Stimulates the penetrated oocyte to complete 2nd meiotic division
• Restores diploid number of chromosomes (46) in the zygote
• Results in variation of the human species through mingling of maternal and paternal
chromosomes
• Determines chromosomal sex of the embryo
 This is determined by the kind of sperm (X or Y) that fertilizes the oocyte
• Metabolic activation of the ootid and initiation of cleavage of the zygote

1st Week: Cleavage
• Cleavage consists of repeated mitotic divisions of the zygote,
resulting in a rapid increase in number of cells (blastomeres)
• It begins approximately 30 hours after fertilization
• Cleavage occurs as the zygote passes along the uterine tube
toward the uterus
• During cleavage, zygote is within the zona pellucida
• These embryonic cells become smaller with each successive
cleavage division
2-cell stage
4-cell stage

1st Week: Cleavage
• After the nine-cell stage, blastomeres tightly align against each
other to form a compact ball of cells
• This phenomenon is called compaction, it is mediated by cell-
surface−adhesion glycoproteins
• When there are 12 to 32 blastomeres, the developing human is
called a morula
• The morula forms approximately 3 days after fertilization as it
enters the uterus
• Morula is still surrounded by the zona pellucida and is about
the same size as the original zygote
Morula

1st Week: Formation of blastocyst
• Shortly after the morula enters the uterus (approx. 4 days
after fertilization), fluid passes from the uterine cavity
through zona pellucida into the morula, and creates a fluid-
filled space
• This fluid-filled space is called blastocystic cavity
• As fluid increases in the blastocystic cavity, it separates the
blastomeres into two parts:
 Trophoblast: A thin, outer cell layer; gives rise to
embryonic part of the placenta
 Embryoblast (Inner cell mass): A group of centrally
located blastomeres; gives rise to the embryo
• At this stage of development, conceptus is called a blastocyst
Blastocyst: External view
Blastocyst: Internal view

1st Week: Formation of blastocyst
• Part of trophoblast covering embryoblast is called
embryonic pole, part covering blastocoel is called
abembryonic pole
• After about 2 days in uterine secretions, zona pellucida
gradually degenerates and disappears
• Shedding of the zona pellucida permits the blastocyst to
increase rapidly in size
• While in the uterus, the embryo derives nourishment
from secretions of the uterine glands
• Early pregnancy factor, an immunosuppressant protein, is secreted by trophoblastic cells and
appears in the maternal serum within 24 to 48 hours after fertilization
• It forms the basis of a pregnancy test during the first 10 days of development

Implantation
• About 6 days after fertilization, blastocyst loosely attaches to
endometrium in a process called implantation
• Implantation usually occurs in the posterior portion of the
fundus or body of the uterus
• Blastocyst orients with the inner cell mass toward the
endometrium
• About 7 days after fertilization, the blastocyst attaches to the
endometrium more firmly, endometrial glands in the vicinity
enlarge, and the endometrium becomes more vascularized
• The blastocyst eventually secretes enzymes and burrows into
the endometrium S14 Embryology lect.BSc.1 18

5 Minutes pause

2nd week of development
• Implantation of the blastocyst is completed during the 2nd week
• It occurs during a restricted time period of 6 to 10 days after ovulation and fertilization
• By end of 1st week, blastocyst is superficially implanted in the compact layer of the
endometrium and is deriving its nourishment from the eroded maternal tissues
• Main events which occur in the 2nd week:
 Development of trophoblast & completion of implantation
 Development of Bilaminar Embryonic Disc
 Development of the Amnion & amniotic cavity
 Development of the yolk sac
 Development of sinusoids
 Development of Extraembryonic Coelom
 Development of the Chorion

2nd week: Development of Trophoblast
• As soon as blastocyst attaches to endometrial
epithelium, the trophoblast proliferates rapidly and
differentiates into 2 layers:
 Cytotrophoblast: An inner layer of
trophoblastic cells that is mitotically active
 Syncytiotrophoblast: An outer layer consisting
of a multinucleated protoplasmic mass with no
clear cell boundaries

• The finger-like processes of syncytiotrophoblast extend through the endometrial epithelium
and invade the connective tissue
• Syncytiotrophoblast produces enzymes that erode maternal tissues, enabling the blastocyst to
“burrow” into the endometrium
• Endometrial cells also assist to control the depth of penetration of the syncytiotrophoblast
• Syncytiotrophoblast begins to form at embryonic
pole, then expands quickly to cover the whole
embryoblast
• At about 9th day the conceptus is completely
embedded in endometrium
• At first the site of implantation is filled by a fibrin
plug which is soon replaced by regenerating
endometrial epithelium

• Syncytiotrophoblast produces a glycoprotein hormone hCG, which enters maternal blood
via isolated cavities (lacunae) in the syncytiotrophoblast
 hCG maintains hormonal activity of the corpus luteum in the ovary during pregnancy
 Form the basis for pregnancy tests. Enough hCG is produced at the end of 2nd week to
give a positive urine pregnancy test

2nd week: Development of Bilaminar Embryonic Disc
• Around day 8, cells of embryoblast differentiate into 2
layers:
 Hypoblast (primitive endoderm)
 Epiblast (primitive ectoderm)
• Cells of the hypoblast and epiblast together form a flat
disc called the bilaminar embryonic disc
• Soon, a small cavity appears within the epiblast and
eventually enlarges to form the amniotic cavity
8 days embryo

2nd week: Development of the Amnion
• As the amniotic cavity enlarges, a single layer of
squamous cells forms a domelike roof above the
epiblast cells called the amnion
• Thus, the amnion forms the roof of the amniotic
cavity, and the epiblast forms the floor
• In later stages of development, embryo folds, amnion
covers the whole embryo, and amniotic cavity houses
the entire embryo

2nd week: Development of the yolk sac
• On the 8th day, cells at the edge of the hypoblast migrate and cover the inner surface of
blastocyst wall
• The migrating cells become squamous (flat) and then form a thin membrane referred to as
the exocoelomic membrane
• Hypoblast and exocoelomic membrane form
wall of the yolk sac, the former blastocyst
cavity during earlier development
• As a result, the bilaminar embryonic disc is
now positioned between the amniotic cavity
and yolk sac

2nd week: Development of the yolk sac
• In human embryos the yolk sac is empty and small, and decreases in size as development progresses
• Yolk sac has several important functions in humans:
 Supplies nutrients to embryo during 2nd and 3rd weeks of development
 It is the source of blood cells from the 3rd to 6th weeks of development
 Contains the 1st cells (primordial germ cells) that will migrate into the developing gonads, and
differentiate into primitive germ cells
 Forms part of the gut (gastrointestinal tract);
 Functions as a shock absorber
 Helps prevent drying out of the embryo

2nd week: Development of sinusoids
• On 9th day, blastocyst becomes completely
embedded in the endometrium
• As syncytiotrophoblast expands, small spaces
called lacunae develop within it
• By 12th day, lacunae fuse to form larger,
interconnecting spaces called lacunar networks

2nd week: Development of sinusoids
• Endometrial capillaries around the developing
embryo dilate to form maternal sinusoids
• As the syncytiotrophoblast erodes some of the
maternal sinusoids and endometrial glands,
maternal blood and secretions from the glands
enter lacunar networks
• This blood nourishes the embryo and takes away
wastes

2nd week: Development of Extraembryonic Coelom
• About 12th day, extraembryonic mesoderm develops
• These mesodermal cells are derived from the yolk sac
and form a connective tissue layer (mesenchyme) around
the amnion and yolk sac
• Soon a number of large cavities develop in the
extraembryonic mesoderm, which then fuse to form a
single, larger cavity called the extraembryonic coelom

12 day embryo

2nd week: Development of the Chorion
• Extraembryonic mesoderm, Cytotrophoblast, and Syncytiotrophoblast form the Chorion
• Chorion surrounds the embryo, and later, the fetus
• The inner layer of chorion eventually fuses with
amnion
• With development of chorion, extraembryonic
coelom becomes the chorionic cavity
• By the end of 2nd week, bilaminar embryonic disc
becomes connected to trophoblast by a band of
extraembryonic mesoderm called the connecting
(body) stalk
• The connecting stalk is the future umbilical cord

2nd week: Summary (week of “TWO’s)
• The 2nd week of development is known as the period of 2’s because:
 Trophoblast differentiates into 2 layers: cytotrophoblast and syncytiotrophoblast
 Embryoblast forms 2 layers: epiblast and hypoblast
 Two cavities form: amniotic cavity and yolk sac

• Recap events of 2nd week – class participation

3rd week of development
• The 3rd week begins a 6-week embryonic period (Period of organogenesis)
• Key events of the 3rd week:
 Gastrulation: formation of 3 primary germ layers (Ectoderm, Mesoderm and
Ectoderm) which lay the foundation for organ development in weeks 4 through 8
 Neurulation: formation of neural tube, the future nervous system
 Development of somites: the future musculoskeletal system
 Development of intraembryonic coelom
 Early development of cardiovascular system
 Development of chorionic villi and placenta

3rd week: Gastrulation
• Gastrulation is the 1st major event of the 3rd week of development
• Occurs at about day 15 after fertilization
• In this process, the bilaminar embryonic disc transforms into a trilaminar embryonic disc
• Trilaminar embryonic disc consists of 3 primary germ layers:
 Ectoderm
 Mesoderm
 Endoderm
• The primary germ layers are the major embryonic tissues from which various tissues and
organs of the body develop

• Gastrulation involves rearrangement and migration of cells from the epiblast
• The 1st evidence of gastrulation is formation of the primitive streak, a faint groove on dorsal
surface of the epiblast that elongates from posterior to anterior part of the embryo
• The primitive streak clearly establishes the head and tail ends of the embryo, and, right and
left sides
• At the head end of the primitive streak a
small group of epiblastic cells forms a
rounded structure called the primitive node

• Following formation of the primitive streak, cells of the epiblast migrate inward below the
primitive streak and detach from the epiblast, a process called Ingression (Invagination)
• Some invaginated cells displace the hypoblast, forming the endoderm
• Other invaginated cells remain between the epiblast and newly formed endoderm to form the
mesoderm
• Cells remaining in the epiblast then form the ectoderm

• Ectoderm and Endoderm are epithelia composed of tightly packed cells
• Mesoderm is a loosely organized connective tissue (mesenchyme)
• As the embryo develops:
 Endoderm becomes epithelial lining of GI tract, respiratory tract, and several other
organs
 Mesoderm gives rise to muscles, bones, and other connective tissues, and
peritoneum
 Ectoderm develops into epidermis of the skin and the nervous system

• About day 16, mesodermal cells from the primitive node migrate toward the head end of the
embryo and form a hollow tube of cells in the midline called the notochordal process
• By days 22–24, the notochordal process becomes a
solid cylinder of cells called the notochord
• Notochord plays an important role in induction, the
process by which one tissue (inducing tissue)
stimulates the development of an adjacent
unspecialized tissue (responding tissue) into a
specialized one
• An inducing tissue usually produces a chemical
substance that influences the responding tissue
• It also forms nucleus pulposus of the intervertebral
discs

• Also at day 16, Two faint depressions appear on the dorsal surface of the embryo where the
ectoderm and endoderm make contact but lack mesoderm between them
• The structure closer to head end is called Oropharyngeal membrane which will breaks down
during 4th week to connect oral cavity to pharynx
• The structure closer to the tail end is called the Cloacal membrane; degenerates during 7th
week to form openings of the anus and urogenital tracts
• When the cloacal membrane appears, wall of the
yolk sac forms a small outpouching called the
allantois that extends into the connecting stalk
• In humans, allantois plays a role in early formation
of blood and blood vessels, and development of the
urinary bladder

SEM of macaque embryo at day 19

Structures Produced by the Three Primary Germ Layers
ENDODERM
Epithelial lining of gastrointestinal tract
And its glands (except the oral cavity
and anal canal)
Epithelial lining of urinary bladder,
gallbladder, and liver
Epithelial lining of pharynx, auditory
(eustachian) tubes, tonsils, tympanic
(middle ear) cavity, larynx, trachea,
bronchi, and lungs
Epithelium of thyroid gland,
parathyroid glands, pancreas, and
thymus
Epithelial lining of prostate and
bulbourethral (Cowper’s) glands,
vagina, vestibule, urethra, and
associated glands such as the greater
(Bartholin’s) vestibular and lesser
vestibular glands
Gametes (sperm and oocytes)
ECTODERM
All nervous tissue
Epidermis of skin
Hair follicles, arrector pili muscles,
Nails,
Epithelium of skin glands (sebaceous
and sudoriferous), and mammary
glands
Lens, cornea, and internal eye
muscles
Internal and external ear
Neuroepithelium of sense organs
Epithelium of oral cavity, nasal
cavity, paranasal sinuses, salivary
glands, and anal canal
Epithelium of pineal gland, pituitary
gland, and adrenal medullae
Melanocytes (pigment cells)
Almost all skeletal and connective
tissue components of the head
Arachnoid mater and pia mater
MESODERM
All skeletal and cardiac muscle
tissue and most smooth muscle
tissue
Most cartilage, bone, and other
connective tissues
Blood, red bone marrow, and
lymphatic tissue
Blood vessels and lymphatic vessels
Dermis of skin
Fibrous tunic and vascular tunic of
eye
Mesothelium of thoracic, abdominal,
and pelvic cavities
Kidneys and ureters
Adrenal cortex
Gonads and genital ducts (except
germ cells)
Dura mater

3rd week: Neurulation
• At day 17, notochord induces
ectodermal cells over it to form the
neural plate
• By the end of 3rd week, lateral edges
of the neural plate become more
elevated and form the neural fold
• The depressed mid-region is called
the neural groove
Day 17
Day 19 Day 20

3rd week: Neurulation
• Neural folds approach each other and fuse, thus
converting the neural plate into a neural tube
• This begins at the middle of the embryo and
progresses toward the head and tail ends
• As the neural tube forms, some ectodermal cells from
the tube migrate to form several layers of cells called
the neural crest
• The process by which the neural plate, neural folds, and neural tube form is called
neurulation
• Neural tube cells then will develop into the brain and spinal cord
• Neural crest cells give rise to all sensory neurons and postganglionic neurons of peripheral
nerves, adrenal medullae, melanocytes (pigment cells) of the skin, arachnoid mater, and
pia mater of the brain and spinal cord, and almost all of the skeletal and connective tissue
components of the head
Day 22

SEM of chick embryo with part of ectoderm removed

3rd week: Development of somites
By about 17th day,
• Mesoderm adjacent to notochord and neural tube
forms paired longitudinal columns of paraxial
mesoderm
•
• Mesoderm lateral to paraxial mesoderm forms paired
cylindrical masses called intermediate mesoderm
• Mesoderm lateral to the intermediate mesoderm
consists of lateral plate mesoderm

3rd week: Development of somites cont ….
• Paraxial mesoderm soon segments into a series of paired,
cube-shaped structures called somites
• Each somite differentiates into 3 regions: a myotome, a
dermatome, and a sclerotome
 Myotomes: develop into skeletal muscles of the neck,
trunk, and limbs
 Dermatomes: develop into connective tissue, including
dermis of the skin
 Sclerotomes: give rise to vertebrae and ribs
• By the end of 5th week, 42–44 pairs of somites are present

3rd week: Development of intraembryonic coelom
• This cavity splits the lateral plate mesoderm into 2 parts:
 Splanchnic mesoderm: forms the heart and visceral layer
of serous pericardium, blood vessels, smooth muscle and
connective tissues of the respiratory and digestive organs,
and visceral layer pleurae and peritoneum
 Somatic mesoderm: gives rise to the bones, ligaments,
blood vessels, and connective tissue of the limbs and the
parietal layer of the serous membrane of the pericardium,
pleurae, and peritoneum
• In the 3rd week, small spaces appear in the lateral plate mesoderm
• These spaces soon merge to form a larger cavity called the intraembryonic coelom

3rd week cont. : Development of Cardiovascular System
• At the beginning of 3rd week, formation of
blood vessels (angiogenesis) begins in the
extraembryonic mesoderm in the yolk sac,
connecting stalk, and chorion
• Heart forms from splanchnic mesoderm
in the head end of embryo on days 18 and
19
• At the same time, blood cells and blood
plasma begin to develop in blood vessels
in the walls of the yolk sac, allantois, and
chorion S14 Embryology lect.BSc.1 51

The cardiogenic field is established in the mesoderm just after gastrulation (~18-19 days) and develops
into a fully functional, multi-chambered heart by the 8th week
angiogenic cell clusters
(angioblasts/hemangioblasts)
(right dorsal aorta)
(right endocardial tube)
blood islands
(developing blood vessels)
cardiogenic field
pericardial cavity
Langman’s fig 12-1

Lateral
folding
• Lateral folding apposes paired heart tube primordia and brings dorsal aortae to midline
• Heart primordia fuse to form tubular heart
Moore & Persaud fig 13-8

3rd week: Development of the Chorionic Villi and Placenta
• By end of the 2nd week, chorionic villi
begin to develop
• These fingerlike projections consist of
chorion (cytotrophoblast &
syncytiotrophoblast) that projects into the
endometrial wall of the uterus

• By the end of 3rd week, blood capillaries
develop in the chorionic villi
• Several lacunar networks join to form
intervillous spaces
• Intervillous spaces bathe the chorionic villi with
maternal blood

• Blood vessels in chorionic villi connect to embryonic heart through the connecting (body)
stalk
• Fetal blood capillaries within the chorionic villi project into the intervillous spaces
• As a result, maternal blood bathes the chorion-covered fetal blood vessels
• Oxygen and nutrients in maternal blood
within intervillous spaces diffuse into
capillaries of the villi, waste products diffuse
in the opposite direction
• Maternal and fetal blood vessels do not join,
and the blood they carry does not mix

Monozygotic twinning typically occurs during cleavage/blastocyst stages

Ectopic Implantation
Implantation somewhere other than
upper portion of uterus
“Rupture” can lead to life-threatening
hemorrhage

What happens if there is “not enough” gastrulation?
Caudal agenesis (sirenomelia) results.
Premature regression of the primitive streak leads to widespread loss of trunk and lower limb
mesoderm.
VATeR association:
• Vertebral defects
• Anal atresia
• Tracheo-esophageal fistula
• Renal defects
VACTeRL association:
those above plus;
• Cardiovascular defects
• Limb (upper) defects

If the primitive streak fails to regress, multipotent primitive streak cells can develop into
multi-lineage tumors (containing ecto-, meso-, and endodermal tissues).
What happens if there is “too much” gastrulation?
Sacrococcygeal teratoma results

Left-Right asymmetry is established at gastrulation
Leftward beating of cilia at node
moves secreted molecules sonic
hedgehog (Shh) & FGF-8 to the left
side of embryo.
Causes left side genes Nodal and
Pitx2 to be expressed which then
pattern developing organs.
If cilia are defective, Shh and Fgf8
can randomly end up on right side,
resulting in reversal of symmetry,
aka situs inversus
(liver on the left, spleen on the
right, etc.)
Situs can be complete (everything
reversed) or partial (only some organs
reversed).

Class recap – events of 3rd week of development

4th week of development
• During 4th week, embryo undergoes very dramatic changes in shape and size
• Size: Rapid growth nearly tripling its size
• Shape: It is converted from a flat, two-dimensional trilaminar embryonic disc to a three-
dimensional cylinder, a process called embryonic folding
• Other events:
 Formation of pharyngeal arches
 Formation of otic and lens placodes
 Formation of limb buds

4th week: Folding of the embryo
• It is conversion of a flat, 2-dimensional trilaminar embryonic disc to a 3-dimensional
cylinder C-shaped tube
• The cylinder consists of endoderm in the center (gut), ectoderm on the outside (epidermis),
and mesoderm in between
Cranio-Caudal folding
Lateral folding

4th week: Folding of the embryo
• It begins at the end of 3rd week, completes at the end of 4th week
• Folding is influenced by:
Rapid increase in longitudinal length due to rapid growth of neural tube and somites
Rapid expansion of amniotic cavity
• Folding occurs in 2 planes:
Median plane: Folding of cranial and caudal parts of the disc (Cranio-caudal folding)
Horizontal plane: Folding of the lateral parts of the disc (Lateral folding)
• Folding in the median plane produces a head fold and a tail fold
• Folding in the horizontal plane forms 2 lateral folds

Craniocaudal folding
Day 28

Lateral folding
22 days
24 days
26 days 28 days

4th week: Results of folding
• Cylindrical appearance: Conversion of disc into cylindrical shape
• Amniotic cavity surrounds all aspects of embryo
• Formation of definitive yolk sac: part of yolk sac outside the embryo in umbilical cord
• Formation of primitive umbilical ring: A defect in anterior abdominal wall that contains connecting
stalk, allantois, and vitello-intestinal duct
• Formation of the gut: Formed by endoderm and part of yolk sac
 Foregut: Formed in head fold, it’s cranial end is closed by oropharyngeal membrane
 Midgut: Mid-portion connected to definitive yolk sac by vitelline duct
 Hindgut: Formed in tail fold, it’s caudal part (called cloaca) is dilated and connected ventrally to
allantois

4th week: Results of folding
• Formation of stomodeum: Ectodermal depression between forebrain bulge and cardiac bulge
• Reversal of positions:
 Heart and pericardium become cranial to septum transversum
 Connecting stalk becomes ventral and more cranial inspite being most caudal
• Formation of mesenteries: Ventral and dorsal mesenteries are formed around gut
• Head fold brings the developing heart and mouth into their adult positions
• Tail fold brings the developing anus into its adult position
• Lateral folds form as the lateral margins of the trilaminar embryonic disc bend ventrally
• As they move toward the midline, the lateral folds incorporate the dorsal part of the yolk sac into the
embryo as the primitive gut
• The primitive gut differentiates into an anterior foregut, an intermediate midgut, and a posterior
hindgut

4th week cont. …..
• Oropharyngeal membrane is located in the head end of the embryo
• It separates the future pharyngeal (throat) region of the foregut from the stomodeum the
future oral cavity.
• Because of head folding, the oropharyngeal membrane moves downward and the foregut and
stomodeum move closer to their final positions.
• When the oropharyngeal membrane ruptures during the 4th week, pharyngeal region of the
pharynx is brought into contact with the stomodeum

4th week: Tail fold
• Last part of hindgut expands into a cavity called the cloaca
• On the outside of the embryo is a small cavity in the tail region called the proctodeum
• Separating the cloaca from the proctodeum is the cloacal membrane
• During embryonic development, the cloaca
divides into a ventral urogenital sinus and a
dorsal anorectal canal.
• As a result of tail folding, the cloacal
membrane moves downward and the
urogenital sinus, anorectal canal, and
proctodeum move closer to their final
positions

4th week: Pharyngeal arches
• In addition to embryonic folding, development of somites, and development of the neural
tube, 5 pairs of pharyngeal (branchial) arches begin to develop on each side of the future
head and neck regions
• These 5 paired structures begin their development on 22nd day and form swellings on the
surface of the embryo
• On the outer surface of pharyngeal region,
each pharyngeal arch is separated by a
groove called a pharyngeal cleft

4th week: Pharyngeal arches
• Each pharyngeal arch consists of an outer covering of ectoderm, and an inner covering of
endoderm, with mesoderm in between
• Within each pharyngeal arch there is an artery, a cranial nerve, cartilage rods that support the
arch, and skeletal muscle tissue that attaches to and moves the cartilage rods
• The pharyngeal clefts meet corresponding
balloon-like outgrowths of the endodermal
pharyngeal lining called pharyngeal pouches

4th week: Formation of otic and lens placodes
• The 1st sign of a developing ear is a thickened area of ectoderm, the otic placode (future
internal ear), which can be distinguished about 22 days after fertilization
• A thickened area of ectoderm called the lens placode, which will become the eye, also
appears at this time

4th week: Formation of limb buds
• By the end of 4th week, lower limb buds develop
• The heart also forms a distinct projection on the
ventral surface of the embryo called the heart
prominence
• At the end of the fourth week the embryo has a
distinctive tail
• By the middle of 4th week, the upper limbs begin their development as outgrowths of
mesoderm covered by ectoderm called upper limb buds

References:
• Principles of Anatomy and Physiology; Gerald Tortora, 13th edition
• The developing human: Clinically oriented Embryology, Keith Moore, 10th edition
• Langman’s medical Embryology, 14th edition
• Larsen’s Human Embryology, 5th edition
• Embryology: an illustrated colour text; Barry Mitchell and Ram Sharma; 2nd edition
• Netter’s Atlas of Human Embryology; Updated edition

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L.12.L13 EMBRYOLOGY 2. FIRST 4 WEEKS.pdf

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