Development of the Embryo during the Third Week

1. Rapid Development:

o The embryo undergoes rapid development from the trilaminar embryonic

disc.

2. Key Features of the Third Week:

o Appearance of Primitive Streak:

 Marks the beginning of the body axis.
 Critical for establishing bilateral symmetry and proper tissue
differentiation.
o Development of Notochord:
 Forms from the mesodermal layer.
 Serves as a crucial structure for signaling and the development of
the vertebral column.
o Differentiation of Three Germ Layers:
 Ectoderm: Will develop into the nervous system, skin, and sensory
organs.
 Mesoderm: Responsible for forming muscles, bones, and the
circulatory system.
 Endoderm: Gives rise to internal organs such as the gut and
respiratory tract.

3. Timing of Development:

o The third week of embryonic development aligns with the week after the
first missed menstrual period.
o This timing corresponds to approximately 5 weeks after the first day of
the last normal menstrual period.

4. Indication of Pregnancy:

o The cessation of menstruation is often the first sign that may indicate
pregnancy.

5. Detection of Pregnancy:
 o At around 5 weeks after the last normal menstrual period, a normal
pregnancy can typically be confirmed through ultrasonography

Gastrulation: Formation of Germ Layers

1. Definition of Gastrulation:

o A formative process that establishes the three germ layers (ectoderm,

mesoderm, and endoderm) which are precursors to all embryonic tissues.
o Involves the establishment of axial orientation in embryos.

2. Transformation of the Embryonic Disc:

o The bilaminar embryonic disc transforms into a trilaminar embryonic disc

(referenced in Fig. 4-2H).

3. Cellular Processes:

o Cell Shape Changes: Cells undergo significant shape alterations to

facilitate movement.
o Rearrangement & Movement: Cellular rearrangements contribute to the
disposition of the germ layers.
o Alterations in Adhesive Properties: Changes in how cells adhere to each
other play a vital role in the process.

4. Significance of Gastrulation:

o Marks the beginning of morphogenesis (development of body form).

o Considered the most significant event of the third week of development.
o During this week, the embryo is designated as a gastrula.

5. Signaling Molecules:

o Key proteins and molecules involved in gastrulation include:

 Bone Morphogenetic Proteins (BMPs)
 Fibroblast Growth Factors (FGFs)
 Sonic Hedgehog (Shh)
 Transforming Growth Factor Inducible Factors (Tgifs)
 Wnts
Origins of Tissues and Organs from Germ Layers
1. Embryonic Ectoderm:

o Develops into:
 Epidermis (skin)
 Central and peripheral nervous systems.
 Eyes and internal ears.
 Neural crest cells.
 Various connective tissues of the head.

2. Embryonic Endoderm:

o Forms:
 Epithelial linings of the respiratory and alimentary (digestive) tracts.
 Glands that open into the gastrointestinal tract.
 Glandular cells of associated organs such as liver and pancreas.

3. Embryonic Mesoderm:

o Gives rise to:

 All skeletal muscles.
 Blood cells.
 Lining of blood vessels.
 Visceral smooth muscles.
 Serosal linings of all body cavities.
 Ducts and organs of the reproductive and excretory systems.
 Most components of the cardiovascular system.
 Connective tissues in the trunk or torso, including:
 Cartilage, bones, tendons, ligaments, dermis, and stroma
(connective tissue) of internal organs.

Primitive Streak
1. Definition and Significance:

o The primitive streak is the first morphological sign of gastrulation.

o It appears on the surface of the epiblast of the bilaminar embryonic disc.
2. Formation:

o By the beginning of the third week, the primitive streak manifests as a

thickened linear band of epiblast.
o It is located caudally in the median plane of the dorsal aspect of the
embryonic disc.

3. Cellular Dynamics:

o The primitive streak results from:

 Proliferation: Increase in the number of cells in the epiblast.
 Movement: Cells migrate toward the median plane of the
embryonic disc.

4. Orientation Establishment:

o The appearance of the primitive streak allows for the identification of:
 Craniocaudal Axis: The head-to-tail orientation of the embryo.
 Cranial and Caudal Ends: Distinction between the head (cranial)
and tail (caudal) regions.
 Dorsal and Ventral Surfaces: Identification of the back (dorsal) and
belly (ventral) sides.
 Right and Left Sides: Establishing bilateral symmetry.

5. Elongation and Node Formation:

o As the primitive streak elongates by the addition of cells at its caudal end,
the cranial end proliferates to form the primitive node.

6. Primitive Groove and Pit:

o A narrow groove, known as the primitive groove, develops within the

primitive streak.
o The groove is continuous with a small depression in the primitive node
called the primitive pit.
o The formation of the primitive groove and pit is due to
the invagination (inward movement) of epiblastic cells.

7. Mesenchyme Formation:

o Shortly after the primitive streak appears, cells leave its deep surface to
form mesenchyme:
  Mesenchyme: An embryonic connective tissue composed of small,
spindle-shaped cells loosely arranged in an extracellular matrix of
sparse collagen (reticular) fibers.
o Functions of mesenchyme:
 Forms supporting tissues of the embryo.
 Contributes to most of the connective tissues in the body.
 Provides the connective tissue framework for glands.
o Some mesenchyme differentiates into mesoblast (undifferentiated
mesoderm), leading to the formation of intraembryonic mesoderm.

ormation of Germ Layers

1. Embryonic Endoderm Formation:

o Cells from the epiblast, as well as those from the primitive node and
other regions of the primitive streak, displace the hypoblast.
o This displacement leads to the formation of embryonic endoderm in the
roof of the umbilical vesicle.

2. Embryonic Ectoderm Formation:

o The cells that remain in the epiblast differentiate into the embryonic
ectoderm.

3. Signaling Molecules and Mesoderm Formation:

o Nodal Factors: These signaling molecules from the transforming growth

factor-β (TGF-β) superfamily are critical for inducing mesoderm
formation.
o Other Signaling Molecules:
 Wnt3a, Wnt5a, and Fibroblast Growth Factors (FGFs) also play a
role in determining the fates of germ cell layers.
o The specification of endoderm involves:
 Transforming Growth Factor-β (Nodal)
 T-box transcription factor (Veg T)
 Wnt signaling pathway

4. Mesenchymal Cell Migration and Differentiation:

 o Mesenchymal cells derived from the primitive streak migrate widely
throughout the embryo.
o These pluripotential cells can differentiate into various cell types,
including:
 Fibroblasts
 Chondroblasts
 Osteoblasts
o Summary: Cells of the epiblast, via gastrulation, give rise to all three germ
layers in the embryo, forming the primordia of all tissues and organs.

Fate of the Primitive Streak

1. Mesoderm Production:

o The primitive streak actively contributes to the formation of mesoderm

through the ingression (entrance) of cells until the early part of the fourth
week.
o After this period, the rate of mesoderm production slows.

2. Diminution of the Primitive Streak:

o The primitive streak gradually diminishes in size and relevance, ultimately

becoming an insignificant structure located in the sacrococcygeal region
of the embryo.

3. Degenerative Changes:

o Typically, the primitive streak undergoes degenerative changes and

disappears by the end of the fourth week of development.

Notochordal Process and Notochord

1. Mesenchymal Cell Migration:

o Some mesenchymal cells migrate through the primitive streak and take
on mesodermal cell fates.
o These cells migrate cranially from the primitive node and primitive pit,
resulting in the formation of a median cellular cord known as
the notochordal process.

2. Formation of Notochordal Canal:

 o The notochordal process soon develops a lumen called the notochordal
canal.
o The notochordal process extends cranially between
the ectoderm and endoderm until it reaches the prechordal plate.

3. Prechordal Plate:

o The prechordal plate consists of a small circular area of columnar

endodermal cells where the ectoderm and endoderm are fused.
o Prechordal mesoderm originates from a mesenchymal population of
neural crest cells located rostrally (toward the head) to the notochord.
o The prechordal plate is crucial as it gives rise to the endoderm of
the oropharyngeal membrane, which is associated with the future oral
cavity.

4. Signaling Role:

o The prechordal plate serves as a signaling center producing factors

like Shh (Sonic Hedgehog) and PAX6, which regulate the development of
craniofacial structures, including the forebrain and eyes.

5. Lateral and Cranial Migration of Mesenchymal Cells:

o Mesenchymal cells from the primitive streak and notochordal process

migrate laterally and cranially, weaving among other mesodermal cells
positioned between the ectoderm and endoderm.
o These migrating cells eventually reach the margins of the embryonic disc.

6. Connection with Extraembryonic Mesoderm:

o The migrating mesenchymal cells are continuous with the extraembryonic

mesoderm that covers the amnion and umbilical vesicle.

7. Cardiogenic Mesoderm Formation:

o Some mesenchymal cells with mesodermal fates migrate cranially on

either side of the notochordal process and around the prechordal plate.
o These cells converge cranially to form the cardiogenic mesoderm in the
cardiogenic area, marking the location where the heart
primordium begins to develop by the end of the third week

Cloacal Membrane
 1. Location and Definition:

o Caudal to the primitive streak, there is a circular area known as

the cloacal membrane.
o This membrane indicates the future site of the anus.

2. Bilaminar Structure:

o The embryonic disc remains bilaminar at the cloacal and oropharyngeal

membranes.
o At these sites, the embryonic ectoderm and endoderm are fused, which
prevents the migration of mesenchymal cells between them.

Intraembryonic Mesoderm Development

3. Mesoderm Separation:
o By the middle of the third week, the intraembryonic
mesoderm separates the ectoderm and endoderm throughout most of
the embryo, except:
 Oropharyngeal Membrane (cranially).
 Median Plane Cranial to the Primitive Node (where the
notochordal process is located).
 Cloacal Membrane (caudally).

Notochord Formation and Function

4. Induction of Notochord:

o Instructive signals from the region of the primitive streak induce

notochordal precursor cells to form the notochord, which is a rod-like
cellular structure.
o The molecular mechanism involves Shh (Sonic Hedgehog) signaling from
the floor plate of the neural tube.

5. Functions of the Notochord:

o Defines the Longitudinal Axis: The notochord establishes the primordial

longitudinal axis of the embryo and provides structural rigidity.
o Signaling Role: It emits signals crucial for the development of:
  Axial Musculoskeletal Structures: Essential for the formation of
the spine and associated structures.
 Central Nervous System (CNS): Necessary signaling for CNS
development.
o Contribution to Intervertebral Discs: The notochordal cells contribute to
the formation of intervertebral discs located between the bodies of
adjacent vertebrae

Notochordal Process Development

1. Initial Elongation:

o The notochordal process elongates through the invagination of cells

from the primitive pit.
o The primitive pit forms an indentation that extends into the notochordal
process, resulting in the development of the notochordal canal.

2. Formation of the Cellular Tube:

o The notochordal process transforms into a cellular tube that stretches

cranially from the primitive node to the prechordal plate.
o Later, the floor of the notochordal process fuses with the
underlying embryonic endoderm.

3. Degeneration and Openings:

o The fused layers gradually degenerate, leading to the formation of

openings in the floor of the notochordal process.
o This allows for communication between the notochordal canal and
the umbilical vesicle.

4. Formation of Notochordal Plate:

o As the openings in the notochordal canal become confluent, the floor of

the canal disappears.
o The remains of the notochordal process form a flattened, grooved
structure known as the notochordal plate.

5. Creation of the Notochord:

 o Starting at the cranial end of the embryo, the cells of the notochordal
plate proliferate and undergo infolding to create the notochord.

6. Persistent Canal:

o The proximal part of the notochordal canal remains temporarily as

the neurenteric canal, which establishes a transitory communication
between the amniotic cavity and the umbilical vesicle.
o As the notochord develops, the neurenteric canal typically obliterates.

7. Detachment from Endoderm:

o Eventually, the notochord detaches from the endoderm of the umbilical

vesicle, allowing the endoderm to become a continuous layer again.

Structure and Functions of the Notochord

8. Location:

o The notochord extends from the oropharyngeal membrane to

the primitive node.

9. Degeneration:

o The notochord degenerates as vertebral bodies form; however, some

portions persist as the nucleus pulposus in each intervertebral disc.

10. Primary Inductor Role:

o The notochord functions as a primary inductor or signaling center in the

early embryo.
o It induces the overlying embryonic ectoderm to thicken and form
the neural plate, which is the primordium of the central nervous system
(CNS)

Allantois Development
1. Appearance:

o The allantois emerges around day 16 as a

small diverticulum (outpouching) from the caudal wall of the umbilical
vesicle.
 o It extends into the connecting stalk of the embryo.

2. Size and Function:

o The allantois remains quite small during development.

o The allantoic mesoderm expands beneath the chorion, forming blood
vessels essential for the placenta.

3. Urachus Formation:

o The proximal part of the original allantoic diverticulum persists as a stalk

called the urachus.
o The urachus extends from the bladder to the umbilical region and plays
a role in fetal development.

4. Adult Remnant:

o In adults, the urachus is represented by the median umbilical ligament.

5. Blood Vessel Development:

o The blood vessels that develop from the allantoic stalk become
the umbilical arteries.
o It is noted that the intraembryonic part of the umbilical veins originates
from a different source.

Neurulation: Formation of Neural Tube

1. Definition of Neurulation:

o Neurulation refers to the processes involved in the formation of the neural

plate, neural folds, and the closure of these folds to form the neural
tube.
o This process is completed by the end of the fourth week with the closure
of the caudal neuropore.

2. Neural Plate Formation:

o As the notochord develops, it induces the overlying embryonic

ectoderm at or near the midline to thicken and form an elongated neural
plate composed of thickened epithelial cells.
 o The neuroectoderm of the neural plate is responsible for giving rise to
the central nervous system (CNS), which includes both
the brain and spinal cord.

3. Additional Derivatives:

o In addition to the CNS, the neuroectoderm also gives rise to various other
structures, such as the retina.

4. Relation to Notochord:

o Initially, the neural plate corresponds in length to the underlying

notochord.
o The neural plate is located rostrally (toward the head) to the primitive
node and dorsally (posterior) to the notochord and adjacent mesoderm.

5. Expansion of the Neural Plate:

o As the notochord continues to elongate, the neural plate broadens,

eventually extending cranially to the oropharyngeal membrane.
o Ultimately, the neural plate extends beyond the initial length of the
notochord

Neural Tube Formation

1. Invagination of Neural Plate:

o Around the 18th day of embryonic development, the neural

plate invaginates along its central axis, forming a longitudinal median
neural groove.
o Neural folds develop on each side of the groove, becoming particularly
prominent at the cranial end of the embryo. This prominence marks the
initial signs of brain development.

2. Fusion of Neural Folds:

o By the end of the third week, the neural folds begin to move towards
each other and fuse, transforming the neural plate into the neural tube.
o The neural tube serves as the primordium (precursor) of the brain
vesicles and spinal cord.

3. Separation from Ectoderm:

 o As the neural folds meet and fuse, the neural tube separates from
the surface ectoderm.

4. Neural Crest Cell Migration:

o Neural crest cells undergo an epithelial-to-mesenchymal transition,

allowing them to migrate away as the neural folds fuse.
o The free edges of the surface ectoderm (now termed nonneural
ectoderm) fuse together, creating a continuous layer over the neural tube
and the dorsal aspect of the embryo.

5. Differentiation of Surface Ectoderm:

o Following the fusion, the surface ectoderm differentiates into

the epidermis, forming the outer layer of the skin.

6. Completion of Neurulation:

o Neurulation is completed during the fourth week of development.

o The process of neural tube formation is complex, involving a cascade of
molecular mechanisms and extrinsic factors that guide cellular
behaviors and transitions

Neural Crest Formation

1. Neuroectodermal Cell Changes:

o As the neural folds fuse to form the neural tube, certain

neuroectodermal cells located along the inner margins of the folds lose
their epithelial affinities and attachments to neighboring cells.
o This transition is crucial for the subsequent formation of the neural crest.

2. Formation of Neural Crest:

o Following the separation of the neural tube from the surface ectoderm,
the migrating neural crest cells form a flattened, irregular mass known as
the neural crest.
o The neural crest is positioned between the neural tube and the overlying
surface ectoderm.

3. Signaling Pathways:
 o Wnt/β-catenin signaling plays a critical role in activating the GBX2
homeobox gene, which is essential for the development of the neural
crest.

4. Separation and Migration:

o The neural crest quickly separates into right and left parts, which migrate
to the dorsolateral regions of the neural tube.
o In these regions, neural crest cells give rise to the sensory ganglia of both
spinal and cranial nerves.

5. Dissemination of Neural Crest Cells:

o Neural crest cells migrate both into and over the surfaces
of somites (blocks of mesoderm).
o While these cells are often challenging to identify, special tracer
techniques have shown that they distribute broadly, typically
along predefined pathways.

6. Regulation of Differentiation and Migration:

o The differentiation and migration of neural crest cells are tightly regulated
by:
 Molecular interactions involving specific genes, such as:
 FOXD3
 SNAIL2
 SOX9
 SOX10
 Various signaling molecules and transcription factors that guide
these processes.

Derivatives and Functions of Neural Crest Cells

1. Ganglia Formation:

o Neural crest cells are responsible for the formation of:

 Spinal ganglia (also known as dorsal root ganglia).
 Ganglia of the autonomic nervous system.
 Ganglia of cranial nerves V (trigeminal), VII (facial), IX
(glossopharyngeal), and X (vagus).
2. Support Structures:

o In addition to ganglia, neural crest cells contribute to:

 The formation of neurolemma sheaths around peripheral nerves.
 The development of the leptomeninges, which includes both
the arachnoid mater and pia mater of the central nervous system.

3. Additional Contributions:

o Neural crest cells also participate in the formation of:

 Pigment cells (melanocytes).
 The suprarenal medulla (adrenal medulla), which produces
adrenaline.
 Various other tissues and organs throughout the body.

4. Establishment of Neural Plate Boundaries:

o Laboratory studies suggest that appropriate cell interactions within the

surface epithelium and between the epithelium and underlying mesoderm
are crucial in:
 Establishing the boundaries of the neural plate.
 Specifying the sites for epithelial–mesenchymal
transformation (EMT), which is essential for neural crest formation.

5. Mediating Signaling Pathways:

o Key signaling pathways involved in these processes include:

 Bone morphogenetic proteins (BMPs).
 Wnt signaling.
 Notch signaling.
 Fibroblast growth factor (FGF) signaling.

6. Guidance of Neural Crest Migration:

o Molecules such as ephrins are critical in guiding specific streams of

migrating neural crest cells, helping them navigate to their appropriate
destinations.

7. Impact of Neural Crest Cell Defects:

 o Many human diseases can arise from defects in the migration and/or
differentiation of neural crest cells, leading to various congenital disorders
and conditions.

Development of Somites
1. Origins of Paraxial Mesoderm:

o In addition to the notochord, cells derived from the primitive

node contribute to the formation of paraxial mesoderm.
o Near the primitive node, this mesoderm appears as a thick, longitudinal
column of cells.

2. Relationship with Intermediate and Lateral Mesoderm:

o Each column of paraxial mesoderm is continuous laterally with

the intermediate mesoderm, which gradually thins into a layer of lateral
mesoderm.
o The lateral mesoderm is in continuity with the extraembryonic
mesoderm covering the umbilical vesicle and amnion.

3. Differentiation into Somites:

o Toward the end of the third week of development, the paraxial mesoderm
differentiates and condenses to form paired structures known as somites.
o Somites develop in a craniocaudal sequence (from head to tail).

4. Location of Somites:

o The somites are located on each side of the developing neural tube.

5. Quantity of Somites:

o Approximately 38 pairs of somites form during the somite period of

human development, which spans from days 20 to 30.
o By the end of the fifth week, the number of somites increases to 42 to 44
pairs.

6. Size and Shape Determination:

o The size and shape of the somites are influenced by cell–cell

interactions within the mesoderm.
 7. Morphology of Somites:

o Somites create distinct surface elevations on the embryo, appearing

somewhat triangular in transverse sections.
o Their prominence during the fourth and fifth weeks of development
makes them important indicators for determining the age of an embryo

Development and Role of Somites

1. Initial Appearance:

o Somites first appear in the future occipital region of the head of the
embryo.
o The appearance of somites progresses in a craniocaudal direction (from
head to tail).

2. Contributions of Somites:

o Somites are crucial for giving rise to:

 Most of the axial skeleton (including vertebrae and ribs).
 Associated musculature, such as skeletal muscles.
 The adjacent dermis of the skin.

3. Location of the First Pair:

o The first pair of somites emerges a short distance caudal (toward the tail)
to the site of the forming otic placode (which contributes to the ear
structures).

4. Motor Axons and Innervation:

o Motor axons from the spinal cord are responsible for innervating muscle
cells in the somites.
o This innervation process requires proper guidance to ensure that axons
reach their appropriate target cells.

5. Molecular Mechanisms of Somite Formation:

o The formation of somites from paraxial mesoderm involves:

 The expression of NOTCH pathway genes (involved in cell
differentiation and communication).
  HOX genes, which play a critical role in determining the identity
and positioning of somites along the body axis.
 Other signaling factors involved in mesoderm development.

6. Preceding Factors in Somite Formation:

o Before somite formation, the expression of forkhead transcription

factors FoxC1 and FoxC2 occurs, which are important for mesoderm
development.

7. Segmental Pattern Regulation:

o The Delta-Notch signaling pathway regulates the craniocaudal segmental

pattern of the somites, helping organize their formation along the embryo.

8. Molecular Oscillator Mechanism:

o A molecular oscillator or clock has been proposed as the mechanism

that underlies the orderly sequencing of somite formation, ensuring the
correct timing and patterning during development.

Development of Intraembryonic Coelom

1. Formation of Coelomic Spaces:

o The intraembryonic coelom (embryonic body cavity) initially appears as

isolated coelomic spaces within the lateral intraembryonic
mesoderm and cardiogenic mesoderm.

2. Coalescence into Coelom:

o These isolated spaces soon coalesce to form a single, horseshoe-shaped

cavity, which is the intraembryonic coelom.

3. Division of Lateral Mesoderm:

o The formation of the intraembryonic coelom divides the lateral mesoderm

into two distinct layers:
 Somatic (Parietal) Layer:
 Located beneath the ectodermal epithelium.
 Continuous with the extraembryonic mesoderm covering
the amnion.
  Splanchnic (Visceral) Layer:
 Located adjacent to the endoderm.
 Continuous with the extraembryonic mesoderm covering
the umbilical vesicle.

4. Formation of Body Walls:

o The somatic mesoderm and the overlying embryonic ectoderm together

form the embryonic body wall, also known as the somatopleure.
o The splanchnic mesoderm and underlying embryonic endoderm combine
to form the embryonic gut, also referred to as the splanchnopleure.

5. Division into Body Cavities:

o During the second month of development, the intraembryonic coelom is

subdivided into three distinct body cavities:
 Pericardial Cavity: Surrounds the heart.
 Pleural Cavities: Surround the lungs.
 Peritoneal Cavity: Encloses the abdominal organs

Early Development of the Cardiovascular System

1. Nutritional Mechanism:

o At the end of the second week, the embryo relies on maternal blood for
nutrition, which is obtained through diffusion across the extraembryonic
coelom and umbilical vesicle.

2. Formation of Blood Vessels:

o At the beginning of the third week, the formation of blood vessels

initiates in:
 The extraembryonic mesoderm of the umbilical vesicle.
 The connecting stalk (the future umbilical cord).
 The chorion (the outermost membrane covering the embryo).

3. Development of Embryonic Blood Vessels:

o Embryonic blood vessels begin to develop approximately 2 days after the

initial formation of vascular structures in the extraembryonic mesoderm.

4. Need for Early Vascularization:

 o The early formation of the cardiovascular system is crucial due to the need
for blood vessels to:
 Supply oxygen and nourishment to the embryo.
 Facilitate the transfer of these needs from the maternal
circulation through the placenta.

5. Uteroplacental Circulation:

o During the third week, a primordial uteroplacental circulation begins to

develop, establishing the connection between maternal blood and the
embryo, ensuring the embryo receives the necessary nutrients and gases.

Vasculogenesis and Angiogenesis

1. Definition of Processes:

o Vasculogenesis:
 The formation of new vascular channels by assembling individual
cell precursors called angioblasts.
o Angiogenesis:
 The formation of new blood vessels
through budding and branching from pre-existing vessels.

2. Initiation of Blood Vessel Formation:

o During the third week, blood vessel formation in the embryo and its
extraembryonic membranes begins when:
 Mesenchymal cells differentiate into endothelial cell
precursors (angioblasts).
 Angioblasts aggregate to create isolated clusters, known
as angiogenic cell clusters or blood islands, associated with
the umbilical vesicle and within the embryo.

3. Formation of Endothelial Channels:

o Within blood islands and endothelial cords:

 Small cavities form through the confluence of intercellular clefts.
 Angioblasts flatten and form endothelial cells, which line the
cavities, creating the endothelium.
 Many endothelium-lined cavities fuse to form a network
of endothelial channels (vasculogenesis).
 4. Continued Vessel Formation:

o Additional blood vessels sprout into adjacent areas through endothelial

budding (angiogenesis) and fuse with existing vessels.
o Mesenchymal cells surrounding these primordial endothelial blood
vessels differentiate into the muscular and connective tissue elements
forming the blood vessel walls.

5. Development of Blood Cells:

o Blood cells develop from specialized endothelial cells (referred to

as hemangiogenic epithelium) as vessels grow on the umbilical
vesicle and the allantois by the end of the third week.
o Additional sites for blood cell development emerge later along the dorsal
aorta.

6. Source of Progenitor Blood Cells:

o Progenitor blood cells also arise directly from hemangiopoietic stem

cells.

7. Hematogenesis:

o Blood formation (hematogenesis) does not commence until the fifth

week of development.
o It begins along the aorta and later occurs in various parts of the
embryonic mesenchyme, predominantly in:
 The liver.
 Subsequently in the spleen, bone marrow, and lymph nodes.

8. Erythrocyte Development:

o Both fetal and adult erythrocytes (red blood cells) derive

from hematopoietic progenitor cells.

Primordial Cardiovascular System

1. Origin of the Heart and Great Vessels:

o The heart and great vessels develop from mesenchymal cells located in
the cardiogenic area.
 2. Formation of Endocardial Heart Tubes:

o During the third week of development, paired, longitudinal

endothelial-lined channels known as endocardial heart tubes begin to
form.
o These tubes fuse to create a single primordial heart tube.

3. Connection to Blood Vessels:

o The tubular heart connects with blood vessels in the embryo, which
integrate the connecting stalk, chorion, and umbilical vesicle to
establish a primordial cardiovascular system.

4. Onset of Circulation:

o By the end of the third week, blood begins to circulate through this
system.

5. Heartbeat Initiation:

o The heart starts to beat around the 21st or 22nd day of embryonic
development.

6. First Functional Organ System:

o The cardiovascular system is recognized as the first organ system to reach

a functional state during embryonic development.

7. Detection of the Embryonic Heartbeat:

o The embryonic heartbeat can be detected using Doppler

ultrasonography during the fourth week, which is approximately 6
weeks after the last normal menstrual period.

Development of Chorionic Villi

1. Initial Formation:

o Primary chorionic villi appear at the end of the second week of embryonic
development.
o Shortly after their appearance, these villi begin to branch.

2. Formation of Secondary Chorionic Villi:

 o Early in the third week, mesenchyme grows into the primary chorionic villi,
forming a core of mesenchymal tissue.
o At this stage, the villi are referred to as secondary chorionic villi, which cover
the entire surface of the chorionic sac.

3. Differentiation of Mesenchymal Cells:

o Some mesenchymal cells within the villi differentiate into capillaries and blood
cells.
o When blood vessels become visible in the villi, they are termed tertiary chorionic
villi.

4. Formation of Arteriocapillary Networks:

o The capillaries in the chorionic villi fuse to form arteriocapillary networks.

o These networks connect with the embryonic heart through vessels that
differentiate in the mesenchyme of the chorion and the connecting stalk.

5. Embryonic Blood Flow:

o By the end of the third week, embryonic blood begins to flow slowly through the
capillaries in the chorionic villi.

6. Nutrient and Gas Exchange:

o Oxygen and nutrients from maternal blood in the intervillous space diffuse
through the walls of the villi into the embryo's blood.
o Conversely, carbon dioxide and waste products from the fetal blood diffuse
through the walls of the chorionic villi into the maternal blood.

7. Formation of the Extravillous Cytotrophoblastic Shell:

o Concurrently, cytotrophoblastic cells of the chorionic villi proliferate and extend

through the syncytiotrophoblast to form an extravillous cytotrophoblastic
shell.
o This shell gradually surrounds the chorionic sac and attaches it to
the endometrium.

8. Types of Villi:

o Villi that attach to maternal tissues through the cytotrophoblastic shell are known
as stem villi (or anchoring villi).
o Villi that grow from the sides of the stem villi are referred to as branch villi.
 o The main exchange of materials between maternal and embryonic blood occurs
through the walls of the branch villi, which are bathed in continually changing
maternal blood in the intervillous space.

Summary of the Third Week

1. Conversion to Trilaminar Disc:

o The bilaminar embryonic disc transitions to a trilaminar embryonic

disc during gastrulation.
o This process begins with the formation of the primitive streak, which appears at
the beginning of the third week as a thickening of the epiblast at the caudal
end of the embryonic disc.

2. Formation of the Primitive Streak:

o The primitive streak results from the migration of epiblastic cells toward
the median plane of the disc.
o Invagination of these cells at the primitive streak generates mesenchymal cells,
which then migrate:
 Ventrally (toward the front),
 Laterally (to the sides),
 Cranially (toward the head).

3. Establishment of Germ Layers:

o As the primitive streak produces mesenchymal cells, the epiblast is referred to

as embryonic ectoderm.
o Some epiblast cells displace the hypoblast, forming the embryonic endoderm.
o The mesenchymal cells that arise from the primitive streak organize into
the intraembryonic mesoderm, which occupies the space between the former
hypoblast and the epiblast cells.

4. Mesoderm Migration:

o Cells of the mesoderm migrate to the edges of the embryonic disc, where they
join the extraembryonic mesoderm that covers the amnion and umbilical
vesicle.

5. Embryonic Disc Appearance:

o By the end of the third week, the embryo presents as a flat, ovoid embryonic
disc.
 o Mesoderm is present between the ectoderm and endoderm across most of the
disc, except at:
 The oropharyngeal membrane,
 The median plane occupied by the notochord,
 The cloacal membrane.
6.
Formation of the Notochordal Process:

o Mesenchymal cells from the primitive streak develop into

the notochordal process, positioned between the embryonic
ectoderm and endoderm.
o The notochordal process extends from the primitive node to
the prechordal plate.
o As the notochordal canal develops, openings form in its floor and coalesce
to create a notochordal plate.

7. Transformation into the Notochord:

o The notochordal plate infolds to form the notochord, which serves as the
primordial axis of the embryo and is critical for the formation of the axial
skeleton (e.g., the vertebral column).

8. Development of the Neural Plate:

o The neural plate appears as a thickening of the embryonic ectoderm,

induced by the underlying notochord.
o A longitudinal neural groove develops within the neural plate, flanked
by neural folds.
o The fusion of these folds results in the formation of the neural tube, which
is the primordium of the central nervous system (CNS).

9. Formation of the Neural Crest:

o As the neural folds fuse to form the neural tube, neuroectodermal

cells form a neural crest, situated between the surface ectoderm and
the neural tube.

10. Development of Paraxial Mesoderm:

o The mesoderm located on either side of the notochord condenses to

form longitudinal columns of paraxial mesoderm.
11. Formation of the Coelom:

o The coelom (body cavity) within the embryo arises as isolated spaces in
the lateral mesoderm and cardiogenic mesoderm.
o These coelomic vesicles eventually coalesce to form a single, horseshoe-
shaped cavity, which will give rise to the body cavities.

12. Development of Blood Vessels:

o Blood vessels are first observed in the walls of the umbilical

vesicle, allantois, and chorion.
o Development of blood vessels within the embryo follows shortly after.
o Fetal erythrocytes (red blood cells) develop from
distinct hematopoietic precursors.

13. Formation of the Primordial Heart:

o The primordial heart exists as paired endocardial heart tubes.

o By the end of the third week, these heart tubes have fused to form
a tubular heart.
o This tubular heart connects to blood vessels in the embryo, umbilical
vesicle, chorion, and connecting stalk, establishing a primordial
cardiovascular system.

14. Chorionic Villi Development:

o Primary chorionic villi develop into secondary chorionic villi as they

gain mesenchymal cores.
o Before the end of the third week, capillaries form in the secondary
chorionic villi, transforming them into tertiary chorionic villi.
o Extensions of cytotrophoblasts from the stem villi join to create
a cytotrophoblastic shell, anchoring the chorionic sac to
the endometrium
o By the end of the third week, this paraxial mesoderm gives rise to somites,
which are crucial for the segmentation of the developing embryo.