Third Week of Development

Gastrulation

During gastrulation, the embryo develops three germ layers (endoderm, mesoderm, and ectoderm) that differentiate into distinct tissues.

Learning Objectives

Describe gastrulation and germ-layer formation

Key Takeaways

Key Points

  • Gastrulation takes place after cleavage and the formation of the blastula. Formation of the primitive streak is the beginning of gastrulation. It is followed by organogenesis—when individual organs develop within the newly-formed germ layers.
  • The ectoderm layer will give rise to neural tissue, as well as the epidermis.
  • The mesoderm develops into somites that differentiate into skeletal and muscle tissues, the notochord, blood vessels, dermis, and connective tissues.
  • The endoderm gives rise to the epithelium of the digestive and respiratory systems and the organs associated with the digestive system, such as the liver and pancreas.

Key Terms

  • somite: One of the paired masses of mesoderm, distributed along the sides of the neural tube, that will eventually become dermis, skeletal muscle, or vertebrae.
  • gastrulation: The stage of embryonic development at which a gastrula is formed from the blastula by the inward migration of cells.
  • notochord: A structure found in the embryos of vertebrates from which the spine develops.
  • epiboly: One
    of many movements in the early embryo that allow for dramatic physical restructuring and is characterized
    by a thinning and spreading of cell layers.

Gastrulation is a phase early in the embryonic development of most animals during which the single-layered blastula is reorganized into a trilaminar (three-layered) structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.

This is a diagram of the formation of the three primary germ layers—ectoderm, mesoderm, and endoderm—that occurs during the first two weeks of development. The embryo at this stage is only a few millimeters in length.

Gastrulation: Formation of the three primary germ layers occurs during the first two weeks of development. The embryo at this stage is only a few millimeters in length.

Gastrulation takes place after cleavage and the formation of the blastula and the primitive streak. It is followed by organogenesis, when individual organs develop within the newly-formed germ layers. Each layer gives rise to specific tissues and organs in the developing embryo.

In amniotes such as humans, gastrulation occurs in the following sequence:

  1. The embryo becomes asymmetric.
  2. The primitive streak forms.
  3. Cells from the epiblast at the primitive streak undergo an epithelial to mesenchymal transition and ingress at the primitive streak to form the germ layers.

The ectoderm gives rise to the epidermis, and also to the neural crest and other tissues that will later form the nervous system. The mesoderm is found between the ectoderm and the endoderm, giving rise to somites.

The somites form muscle, the cartilage of the ribs and vertebrae, the dermis, the notochord, blood and blood vessels, bone, and connective tissue.

The endoderm gives rise to the epithelium of the digestive and respiratory systems, and the organs associated with the digestive system, such as the liver and pancreas. Following gastrulation, the cells in the body are either organized into sheets of connected cells (as in epithelia), or as a mesh of isolated cells, such as mesenchyme.

The molecular mechanism and timing of gastrulation is different in different organisms. However, some common features of gastrulation across triploblastic organisms include:

  • A change in the topological structure of the embryo, from a simply connected surface (sphere-like), to a non-simply connected surface (torus-like)
  • The differentiation of cells into one of three types (endodermal, mesodermal, or ectodermal).
  • The digestive function of a large number of endodermal cells.

Although gastrulation patterns exhibit enormous variation throughout the animal kingdom, they are unified by the five basic types of cell movements that occur during gastrulation:

  1. Invagination
  2. Involution
  3. ingression
  4. Delamination
  5. Epiboly

Neurulation

Following gastrulation, the neurulation process develops the neural tube in the ectoderm, above the notochord of the mesoderm.

Learning Objectives

Outline the process of neurulation

Key Takeaways

Key Points

  • The notochord stimulates neurulation in the ectoderm after its development.
  • The neuronal cells running along the back of the embryo form the neural plate, which folds outward to become a groove.
  • During primary neurulation, the folds of the groove fuse to form the neural tube. The anterior portion of the tube forms the basal plate, the posterior portion forms the alar plate, and the center forms the neural canal.
  • The ends of the neural tube close at the conclusion of the fourth week of gestation.

Key Terms

  • basal plate: In the developing nervous system, this is the region of the neural tube ventral to the sulcus limitans. It extends from the rostral mesencephalon to the end of the spinal cord and contains primarily motor neurons.
  • neurulation: The process that forms the vertebrate nervous system in embryos.
  • alar plate: The alar plate (or alar lamina) is a neural structure in the embryonic nervous system, part of the dorsal side of the neural tube, that involves the communication of general somatic and general visceral sensory impulses. The caudal part later becomes the sensory axon part of the spinal cord.
  • notochord: Composed of cells derived from the mesoderm, this provides
    signals to the surrounding tissue during development.

Neurulation is the formation of the neural tube from the ectoderm of the embryo. It follows gastrulation in all vertebrates. During gastrulation cells migrate to the interior of the embryo, forming the three germ layers: the endoderm (the deepest layer), the mesoderm (the middle layer), and the ectoderm (the surface layer) from which all tissues and organs will arise.

In a simplified way, it can be said that the ectoderm gives rise to skin and the nervous system, the endoderm to the intestinal organs, and the mesoderm to the rest of the organs.

After gastrulation, the notochord—a flexible, rod-shaped body that runs along the back of the embryo—is formed from the mesoderm. During the third week of gestation the notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm.

This results in a strip of neuronal stem cells that runs along the back of the fetus. This strip is called the neural plate, and it is the origin of the entire nervous system.

The neural plate folds outwards to form the neural groove. Beginning in the future neck region, the neural folds of this groove close to create the neural tube (this form of neurulation is called primary neurulation).

The anterior (ventral or front) part of the neural tube is called the basal plate; the posterior (dorsal or rear) part is called the alar plate. The hollow interior is called the neural canal. By the end of the fourth week of gestation, the open ends of the neural tube (the neuropores) close off.

This is a series of illustrations of transverse sections that show the progression of the neural plate into the neural tube. The first illustration shows the neural plate as flat, laying atop the mesoderm and notochord. The second shows the neural plate bending down, with the tow tends joining at the neural plate borders, which are now referred to as the neural crest. The third shows the closure of the neural tube and how this disconnects the neural crest from the epidermis. The neural crest cells differentiate to form most of the peripheral nervous system. Finally, the notochord degenerates and other mesoderm cells differentiate into the somites.

Neurulation: Transverse sections that show the progression of the neural plate into the neural tube.

Secondary neurulation of vertebrates occurs when primary neurulation terminates. It is the process by which the neural tube at the lower levels and the caudal to the mid-sacral region is formed.

In general, it entails the cells of the neural plate forming a cord-like structure that migrates inside the embryo and hollows to form the tube. Each organism uses primary and secondary neurulation to varying degrees (except fish, which use only secondary neurulation).

Clinical Example

Spina bifida is a developmental congenital disorder caused by the incomplete closing of the neural tube during neurulation.

This is an illustration of a child with spina bifida. An open defect is seen at the base of the child's spine.

Spina bifida: An illustration of a child with spina bifida

Somite Development

Somites develop from the paraxial mesoderm and participate in the facilitation of multiple developmental processes.

Learning Objectives

Describe the functions of somites

Key Takeaways

Key Points

  • The paraxial mesoderm is distinct from the mesoderm found more internally in the embryo.
  • Alongside the neural tube, the mesoderm develops distinct paired structures called somites that develop into dermis, skeletal muscle, and vertebrae.
  • Each somite has four compartments: the sclerotome, myotome, dermatome, and the syndetome. Each becomes a specific tissue during development.

Key Terms

  • neural crest cells: A transient, multipotent, migratory cell population that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage, bone, smooth muscle, peripheral and enteric neurons, and glia.
  • conceptus: The fetus or embryo, including all the surrounding tissues protecting and nourishing it during pregnancy.
  • somite: One of the paired masses of mesoderm, distributed along the sides of the neural tube, that will eventually become dermis, skeletal muscle, or vertebrae.

Intraembryonic Coelom Development

In the development of the human embryo the intraembryonic coelom (or somatic coelom) is a portion of the conceptus that forms in the mesoderm. During the second week of development the lateral mesoderm splits into a dorsal somatic mesoderm (somatopleure) and a ventral splanchnic mesoderm (splanchnopleure).

By the third week of development, this process gives rise to a cavity between the somatopleure and splanchnopleure referred to as the intraembryonic celom. This space later gives rise to both the thoracic and abdominal cavities.

Somite Development

In the developing vertebrate embryo, somites are masses of mesoderm that can be found distributed along the two sides of the neural tube. They will eventually become dermis (dermatome), skeletal muscle (myotome), vertebrae (sclerotome), and tendons and cartilage (syndetome).

The mesoderm found lateral to the neural tube is called the paraxial mesoderm. It is separate from the chordamesoderm underneath the neural tube. The paraxial mesoderm is initially called the unsegmented
mesoderm in vertebrates, but is called the segmented mesoderm in chick embryos.

This is drawing of a dorsal view of a human embryo. The repetitive somites are marked with the older term primitive segments.

Somites: A dorsal view of a human embryo. The repetitive somites are marked with the older term primitive segments.

As the primitive streak regresses and the neural folds gather preceding the formation of the neural tube, the paraxial mesoderm divides into blocks called somites. Somites play a critical role in early development by participating in the specification of the migration paths of neural crest cells and spinal nerve axons.

Later in development, somites separate into four compartments:

Dermatome

The dermatome is the dorsal portion of the paraxial mesoderm somite. In the human embryo it arises in the third week of embryogenesis.

The dermatomes contribute to the skin, fat, and connective tissue of the neck and of the trunk, though most of the skin is derived from the lateral plate mesoderm.

Myotome

The myotome is that part of a somite that forms the muscles. Each myotome divides into an epaxial part (epimere), at the back, and a hypaxial part (hypomere) at the front.

The myoblasts from the hypaxial division form the muscles of the thoracic and anterior abdominal walls. The epaxial muscle mass loses its segmental character to form the extensor muscles of the neck and trunk of mammals.

Sclerotome

The sclerotome forms the vertebrae and the rib cartilage and part of the occipital bone. It forms the musculature of the back, the ribs, and the limbs.

Syndetome

The syndetome forms the tendons and some blood vessels.

Development of the Cardiovascular System

The circulatory system develops initially via vasculogenesis, with the arterial and venous systems developing from distinct embryonic areas.

Learning Objectives

Outline the development of the cardiovascular system

Key Takeaways

Key Points

  • The aortic arches are a series of six, paired, embryological vascular structures that give rise to several major arteries. The first and second arches disappear early. The third arch becomes the carotid artery.
  • The fourth right arch forms the right subclavian artery, while the fourth left arch forms the arch of the aorta. The fifth arch disappears on both sides.The proximal part of the sixth right arch persists as the proximal right pulmonary artery. The sixth left arch gives off the left pulmonary artery.
  • Approximately 30 posterolateral branches arise off the dorsal aortae and will form the intercostal arteries, the upper and lower extremity arteries, the lumbar arteries, and the lateral sacral arteries. The lateral branches of the aorta form the definitive renal, suprarenal, and gonadal arteries.
  • The ventral branches consist of the vitelline and umbilical arteries. The vitelline arteries form the celiac, and superior and inferior mesenteric arteries of the gastrointestinal tract. After birth, the umbilical arteries will form the internal iliac arteries.
  • The venous system develops from the vitelline veins, umbillical veins, and the cardinal veins, all of which empty into the sinus venosus.

Key Terms

  • sinus venosus: A large quadrangular cavity that precedes the atrium on the venous side of the chordate heart. In humans, it exists distinctly only in the embryonic heart, where it is found between the two venae cavae.
  • aortic arches: Also known as pharyngeal arch arteries, this is a series of six, paired, embryological vascular structures that give rise to several major arteries. They are ventral to the dorsal aorta.
  • cardinal vein: The precardinal veins or anterior cardinal veins contribute to the formation of the internal jugular veins and, together with the common cardinal vein, form the superior vena cava. In an anastomosis by anterior cardinal veins, the left brachiocephalic vein is produced.

Vasculogenesis

The human arterial system originates from the aortic arches and from the dorsal aortae starting from week 4 of embryonic life.
The development of the circulatory system initially occurs by the process of vasculogenesis, the formation of new blood vessels when there are no preexisting ones.

This is a drawing of a profile view of a human embryo estimated at twenty or twenty-one days old. The six aortic arches are identified.

Embryonic cardiovascular system: A profile view of a human embryo estimated at twenty or twenty-one days old.

Vasculogenesis is when endothelial precursor cells (angioblasts) migrate and differentiate in response to local cues (such as growth factors and extracellular matrix) to form new blood vessels. The human arterial and venous systems develop from different embryonic areas.

Aortic Arches

The aortic arches—or pharyngeal arch arteries—are a series of six, paired, embryological vascular structures that give rise to several major arteries. They are ventral to the dorsal aorta and arise from the aortic sac.

Arches 1 and 2

This is a schematic drawing of the aortic arches and their arterial destinations.

Aortic arches: A schematic of the aortic arches and their arterial destinations.

The first and second arches disappear early, but the dorsal end of the second gives origin to the stapedial artery, a vessel that atrophies in humans, but persists in some mammals. It passes through the ring of the stapes and divides into supraorbital, infraorbital, and mandibular branches that follow the three divisions of the trigeminal nerve.

The infraorbital and mandibular branches arise from a common stem, the terminal part of which anastomoses with the external carotid. On the obliteration of the stapedial artery, this anastomosis enlarges and forms the internal maxillary artery; the branches of the stapedial artery are now branches of this vessel.

The common stem of the infraorbital and mandibular branches passes between the two roots of the auriculotemporal nerve and becomes the middle meningeal artery. The original supraorbital branch of the stapedial artery is represented by the orbital branches of the middle meningeal artery.

Arches 3 and 4

The third aortic arch constitutes the commencement of the internal carotid artery, and is named the carotid arch. The fourth right arch forms the right subclavian artery as far as the origin of its internal mammary branch. The fourth left arch constitutes the arch of the aorta between the origin of the left carotid artery and the termination of the ductus arteriosus.

Arches 5 and 6

The fifth arch disappears on both sides.The proximal part of the sixth right arch persists as the proximal part of the right pulmonary artery, while the distal section degenerates. The sixth left arch gives off the left pulmonary artery and forms the ductus arteriosus.

This duct remains during fetal life, but closes within the first few days after birth due to increased O2 concentration. This causes the production of bradykinin which causes the ductus to constrict, occluding all flow. Within one to three months, the ductus is obliterated and becomes the ligamentum arteriosum.

Aortic Branches

The dorsal aortae are initially bilateral and then fuse to form the definitive dorsal aorta. Approximately 30 posterolateral branches arise off the aorta and will form the intercostal arteries, upper and lower extremity arteries, lumbar arteries, and the lateral sacral arteries.

The lateral branches of the aorta form the definitive renal, suprarenal, and gonadal arteries. Finally, the ventral branches of the aorta consist of the vitelline arteries and umbilical arteries.

The vitelline arteries form the celiac, and superior and inferior mesenteric arteries of the gastrointestinal tract. After birth, the umbilical arteries will form the internal iliac arteries.

The human venous system develops mainly from the vitelline, umbilical, and cardinal veins, all of which empty into the sinus venosus. The venous system arises during the fourth to eighth weeks of human development.

Clinical Example

Most defects of the great arteries arise as a result of the persistence of aortic arches that normally should regress or due to the regression of arches that normally should not.

A double aortic arch occurs with the development of an abnormal right aortic arch, in addition to the left aortic arch, forming a vascular ring around the trachea and esophagus, which usually causes difficulty breathing and swallowing.

Occasionally, the entire right dorsal aorta abnormally persists and the left dorsal aorta regresses. In this case, the right aorta will have to arch across from the esophagus, causing difficulty breathing or swallowing.

Chorionic Villi and Placental Development

In the placenta, chorionic villi develop to maximize surface-area contact with the maternal blood for nutrient and gas exchange.

Learning Objectives

Summarize the development of the chorionic villi and placenta

Key Takeaways

Key Points

  • Chorionic villi invade and destroy the uterine decidua while at the same time they absorb nutritive materials from it to support the growth of the embryo.
  • The villi begin primary development in the fourth week, becoming fully vascularized between the fifth and sixth weeks.
  • Placental development begins with implantation of the blastocyst; this leads to its differentiation into several layers that allow nutrient, gas, and waste exchange to the developing embryo and fetus —as well as forming a protective barrier.

Key Terms

  • chorion: The protective and nutritive membrane that attaches higher vertebrate fetuses to the uterus.
  • uterine decidua: The term for the uterine lining (endometrium) during a pregnancy, which forms the maternal part of the placenta. It is formed under the influence of progesterone and forms highly characteristic cells.
  • chorionic villi: These sprout from the chorion in order to give a maximum area of contact with the maternal blood.
  • placenta: A vascular organ present only in the female during gestation. It supplies food and oxygen from the mother to the fetus, and passes back waste. It is implanted in the wall of the uterus and links to the fetus through the umbilical cord. It is expelled after birth.

Chorionic Villi

Chorionic villi sprout from the chorion after their rapid proliferation in order to give a maximum area of contact with the maternal blood. These villi invade and destroy the uterine decidua while at the same time they absorb nutritive materials from it to support the growth of the embryo.

This is a schematic drawing of a chorionic artery. It shows the chorionic villi connecting to the maternal vessels.

Chorionic artery: An image showing the chorionic villi and the maternal vessels.

During the primary stage (the end of fourth week), the chorionic villi are small, nonvascular, and contain only the trophoblast. During the secondary stage (the fifth week), the villi increase in size and ramify, while the mesoderm grows into them; at this point the villi contain trophoblast and mesoderm.

During the tertiary stage (fifth to sixth week), the branches of the umbilical vessels grow into the mesoderm; in this way, the chorionic villi are vascularized. At this point, the villi contain trophoblast, mesoderm, and blood vessels.

Embryonic blood is carried to the villi by the branches of the umbilical arteries. After circulating through the capillaries of the villi, it is returned to the embryo by the umbilical veins. Chorionic villi are vital in pregnancy from a histomorphologic perspective and are, by definition, products of conception.

Placenta

The placenta is a fetally derived organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother’s blood supply. The placenta begins to develop upon implantation of the blastocyst into the maternal endometrium.

The placenta functions as a fetomaternal organ with two components: the fetal placenta (chorion frondosum), which develops from the same blastocyst that forms the fetus; and the maternal placenta (decidua basalis), which develops from the maternal uterine tissue.

The outer layer of the blastocyst becomes the trophoblast, which forms the outer layer of the placenta. This layer is divided into two further layers: the underlying cytotrophoblast layer and the overlying syncytiotrophoblast layer.

The latter is a multinucleated, continuous cell layer that covers the surface of the placenta. It forms as a result of the differentiation and fusion of the underlying cytotrophoblast cells, a process that continues throughout placental development. The syncytiotrophoblast (otherwise known as syncytium) thereby contributes to the barrier function of the placenta.

This is a color image illustrating the placenta and chorionic villi. The umbilical cord is seen connecting the fetus to the placenta.

Placenta: Image illustrating the placenta and chorionic villi. The umbilical cord is seen connected to the fetus and the placenta.