THE THIRD WEEK OF DEVELOPMENT

This week is characterized by several processes:

- Gastrulation
- Neurulation and formation of neural crests
- Development of somites
- Formation of the intraembryonic coelom
- Formation of the blood and circulatory system

THE GASTRULATION
Is the process by which the bilaminar germ disc (epiblast and hypoblast) become a trilaminar germ
disc (endoderm, mesoderm and ectoderm), between the 15th and the 20th day.
In this period appears in the maternal blood a protein specific for human species named human
chorionic gonadotropin (it is a marker for the pregnancy diagnosis).
The beginning of the gastrulation is marked by the agglomeration of the epiblastic cells in the caudal
region of the germ disc (at the opposite pole of the prechordal plate); this agglomeration of cells
develop a central groove, which become the primitive streak, on the surface of the epiblast. The
cephalic end of the streak, the primitive node, consists of a slightly elevated area surrounding the
small primitive pit.
In this week, the development of the embryo is predominant on the cranial pole of the germ disc.

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 Cells of the epiblast migrate toward the primitive streak and primitive node. These epiblastic
cells divide and migrate between the two embryonic layers (epiblast and hypoblast). Once the cells
are invaginated, some displace the hypoblast, creating the embryonic endoderm, and others come to
lie between the epiblast and newly created endoderm to form mesoderm. Cells remaining in the
epiblast then form ectoderm.
Thus, the epiblast, through the process of gastrulation, is the source of all of the germ layers
and cells in these layers will give rise to all of the tissues and organs in the embryo. In this stage,
when the mesoderm appears, the germ disc become trilaminar, and the three layers are endoderm,
mesoderm and ectoderm.
The mesoderm lies on the entire length of the germ disc, between the epiblast and the
hypoblast, except the prechordal plate and the cloacal membrane which appear at the caudal end of
primitive streak (is similar in structure to the oropharyngeal membrane, consists of tightly adherent
ectoderm and endoderm cells with no intervening mesoderm).
In the 16th day, from the primitive node an invagination like a glove finger moves forward
cranially in the midline until it reaches the prechordal plate. This is the notochordal process; at the
beginning it is a canal, and later it become the notochordal plate. In this moment, the yolk sac
communicates with the amniotic cavity by neurenteric canal (the point where the primitive pit forms
an indentation in the epiblast).
The cells of the notochordal plate proliferate and detach from the endoderm. After that, they form a
solid cord of cells, the definitive notochord which underlies the neural tube and is a signalling centre
for inducing the axial skeleton. It lies between the primitive node and the prechordal plate.

THE NEURULATION
Under the inductor influence of the notochord and the paraxial mesoderm, the ectoderm
situated dorsally to the notochord become thicker and is named the neural plate. This neural plate
and the notochord lengthen to the oropharyngeal membrane. They are the precursor for the central
nervous system and spinal cord.
In the 18th day, as the neural plate lengthens, its lateral edges elevate to form neural folds,
and the depressed midregion forms the neural groove. The neural folds are taller in the cephalic
extremity, forming the cerebral folds. Gradually, to the end of the third week, the neural folds
approach each other in the midline, where they fuse. Fusion begins in the cervical region and proceeds
cranially and caudally. As a result, the neural tube is formed. Until fusion is complete, the cephalic
and caudal ends of the neural tube communicate with the amniotic cavity by way of the anterior
(cranial) and posterior (caudal) neuropores.
The closure of posterior neuropore represents the end of the neurulation.

FORMATION OF THE NEURAL CRESTS

The neural crests are formed by the ectodermal cells during the fusion of neural folds; they
are cellular masses situated between the neural tube and the ectoderm around it. As the neural folds
elevate and fuse, cells at the lateral border (crest of the neuroectoderm) begin to dissociate from their
neighbours and migrate along several pathways in the body.
From the neural crests appear: spinal ganglia, neurons for cranial ganglia of the V, VII, IX, X
cranial nerves, Schwann sheath, pia mater, arachnoid, etc.

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Derivatives of the mesodermal germ layer (FORMATION OF THE SOMITES)
In the 17th day, the mesoderm around the neural tube and notochord divides into three
segments: the paraxial mesoderm, intermediate mesoderm and lateral mesoderm.
Cells close to the midline proliferate and form a thickened plate of tissue known as paraxial
mesoderm. Approximately in the 20th day the paraxial mesoderm begins to be organized into
segments, named somites, and their formation proceeds cephalocaudally.
In the end, there will be 42-44 somites arranged on both sides of median line: 4 occipital, 8 cervical,
12 thoracic, 5 lumbar, 5 sacral, 8-10 coccygeal. The first occipital somites and 5-7 coccygeal somites
disappear, while the remaining somites form the axial skeleton.
From somites derive:

- The most part of the head and trunk skeleton

- The muscles of the head and trunk
- The dermis of the skin

Intermediate mesoderm, which temporarily connects paraxial mesoderm with the lateral
plate, differentiates into urogenital structures.

FORMATION OF THE INTRAEMBRYONIC COELOM

In the lateral mesoderm appear spaces that will fuse and form a cavity: the intraembryonic
coelom. This cavity splits the lateral mesoderm into two layers:

- Dorsal: A parietal (somatic) layer: together with the overlying ectoderm forms the
somatopleure (form thin membranes, the mesothelial membranes, or serous membranes ,
which will line the peritoneal, pleural, and pericardial cavities and secrete serous fluid )
- Anterior: A visceral (splanchnic) layer : together with embryonic endoderm forms the
splanchnopleure (form a thin serous membrane around each organ)

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FORMATION OF BLOOD AND BLOOD VESSELS
Between the 13-15th day begins the angiogenesis, initial into the extraembryonic mesoderm,
and then into the intraembryonic mesoderm.
Some mesenchyme cells (hemangioblasts) proliferate and form masses of cells and cellular cords
named blood islands. Inside the islands appear spaces that will form the lumen of the future vessel
and the hemangioblasts go to the periphery and form the endothelium. In the end results a canalicular
network formed by the primitive endothelial ducts.
The endothelium that is formed will secrete sanguine plasma. The blood cells will be formed starting
with the 5th week.
To the end of the 3rd week the endocardial tube is formed, and in the 21 day, this tube is connected
to the intraembryonic and extraembryonic blood vessels. From this moment starts the sanguine
circulation.
The circulatory system is the first functional system at the end of the 3rd week.

 Mesoderm refers to cells derived from the epiblast and extraembryonic tissues. Mesenchyme
refers to loosely organized embryonic connective tissue regardless of origin.

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 THE FOURTH TO EIGHTH WEEK

This period is characterized by disc bending processes. Through this processes, the disc
changes the longitudinal and transversal axes, and the embryonic disc is transformed into a tubular
formation named embryo.

In this period appear the organ primordia.

The bending processes have two causes:

- Accelerated growing rhythm of the germ disc

- The neural tube, which adapts its form to the space that it has inside the disc.

The disc bending determine narrowing of the communication between the embryo and yolk sac, and
thus appears the primitive umbilical cord.
The embryonic disc is transformed into a rounded, elongated body, that has a comma shape (,) with
its cephalic extremity well developed. The growth of the cephalic plate invaginates the oropharyngeal
membrane, generating the appearance of primitive mouth (the stomodeum - the primitive oral cavity)
which is situated between the brain and the cardiac prominence.
The slower growth of the caudal plate invaginates the cloacal membrane, forming a depression named
the proctodeum (the lower part of the anal canal)
The growth of the lateral plates develop the antero-lateral wall of the body, which incorporates the
cardiogenic region (the heart bulge).
The yolk sac is separated into an extraembryonic part: the definitive yolk sac, and an intraembryonic
part: the primitive gut.

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The development of the organ primordia
Organogenesis occurs in the 4th to 8th week. In this period the heart is formed, and for this reason an
exposure to theratogenic agents will determine congenital malformations of the heart (it is a critical
period of the pregnancy).
In the 4th week, on the dorsal surface of the embryo protrudes the somites, the neural tube is closed
only at this level, and has an anterior and posterior neuropores.
In the 24th day, the first two pharyngeal (brachial) arches appear (mandibular arch and hyoid arch),
and the heart protrudes on the ventral (anterior) surface of the embryo. The brachial arches are
precursors for many structures.
In the 26th day, the anterior neuropore closes and the anterior brain protrudes, the embryo has a “C”
form. Also, in this day the upper limb buds and the otic placodes appear.

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In the 28th day appear the lower limb buds and lens placodes. The dimension of caudal extremity
(the tail) of the embryo and the somites of this region regress.

The 5th week is characterized by the accelerated growing rhythm of the head, which is in contact with
the cardiac prominence.
In the 29th day the limb buds are well developed, the upper limb buds are situated posteriorly to the
cardiac prominence, at the level of the 4-7th somites, which explains their innervation by the brachial
plexus. The lower limb buds are situated at the level of the lumbar and the first sacral somites. To the
end of the 5th week, on the limb buds appear the paddles (flatten terminal portion).
In the 6th week:

- The head is very big compared to the rest of the body; the cervical curvature (flexure)
appears.
- The trunk and the neck are deflected
- The ear pavilion and external acoustic meat appear.
- The limbs are segmented, and thus appear: the elbow, the knee and digital grooves.

In the 7th week:

- The fingers are differentiated

- The gut herniates into the extraembryonic coelom of the umbilical cord

In the 8th week:

- The head is round, deflected and represents one half of the embryo’s length.
- The nuchal region appears
- In this week appear: the vascular plexus of the scalp, eyelids and the ears
- The caudal region (the tail) of the embryo disappear and the general aspect of the embryo
become human.

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From the 9th week to the birth, the fetal period is characterized by:

- Weight gain, in the last weeks of pregnancy

- The maturation of the tissues and organs
- The human appearance is finished
- The heart increases in length

The derivatives of the three embryonic layers:

a. The derivatives of the endoderm:
- The epithelium of the gastrointestinal tract and respiratory system.
- The parenchyma of the palatine tonsils, thyroid gland, parathyroid glands, thymus, liver,
pancreas.
- The epithelium of the urinary bladder, urethra, vagina.
- The epithelium of the tympanic cavity and auditory tube (Eustachio)

b. The derivatives of the ectoderm:

- The epidermis and its derivatives (hair, nails, sweat glands, sebaceous glands), parotid glands,
mammary gland.
- Central nervous system, peripheral nervous system, pituitary gland, enamel of the teeth.

c. The derivatives of the mesoderm:

- The connective tissue, cartilaginous tissue and bone tissue
- The smooth muscles and the striated musculature
- Sanguine vessels, lymphatic vessels, the cells and elements of the blood
- Adrenocortical glands, dentine, cement
- The heart, kidneys, genital glands
- The pericardium, pleura, peritoneum.