Embryogenesis is the process of embryonic development occurring in the first eight weeks after fertilization. After implantation of the blastocyst in the endometrium, the embryo consists of the embryoblast and the trophoblast. While the embryoblast further develops into different structures of the body, the trophoblast is mainly involved in the development of the placenta. The amniotic cavity, yolk sac, extraembryonic mesoderm, and the chorionic cavity develop during the second week. In weeks 3 and 4, the bilaminar disc differentiates into a trilaminar embryonic disc through the process of gastrulation. A number of structures develop from the three germ layers. The nervous system also develops during weeks 3 and 4 through the process of neurulation. Weeks 5–8 are mainly characterized by organogenesis and continued differentiation of embryonic tissue.
2nd week of embryonic development (days 8–14)
- Embryoblast → bilaminar disc (epiblast and hypoblast)
- Trophoblast → chorionic cavity (lined by extraembryonic mesoderm) → cytotrophoblast and syncytiotrophoblast → fetal component of the placenta
3rd and 4th week of embryonic development (days 15–28)
- Gastrulation: Epiblast cells → primitive streak → trilaminar disc (endoderm, mesoderm, ectoderm)
- Notogenesis: axial mesoderm → notochord → induces development of neural plate from ectoderm
- Neurulation: ectoderm → neural plate → neural tube with neural pores, neural crest
- Branchial apparatus → pharyngeal arches, pharyngeal pouches, pharyngeal grooves
- Aortic arches
- Differentiation of the germinal disc
- Primitive circulation with a tubular heart and initial intraembryonic blood vessels
The embryo is extremely susceptible to teratogens from week 3 to week 8, when the process of organogenesis occurs.
5th–8th week of embryonic development (days 29–56)
Weeks 5–8 of embryogenesis mainly involves organogenesis and continued differentiation of the embryo. Organogenesis is complete by the end of week 8. In the subsequent fetal period, the fetus grows and develops.
|Week 7|| |
|Week 8|| |
In the 2nd week of embryonic development (days 8–14), the embryoblast differentiates into two layers (epiblast and hypoblast), termed the bilaminar disc. After formation of the amniotic cavity and yolk sac, the bilaminar disc is sandwiched between them.
Embryoblast → bilaminar disc
- Epiblast: columnar cells adjacent to amnioblasts → form the amniotic cavity → forms the embryo (begins the 3rd week of embryonic development)
- Hypoblast: cuboidal cells adjacent to the blastocyst cavity; (blastocoel) : forms yolk sac, lining of chorionic cavity
- Fusion of epiblast and hypoblast → prechordal plate → mouth
All three germ layers (ectoderm, mesoderm, and endoderm), as well as the amniotic cavity and therefore the entire embryonic tissue, arise from the epiblast. The extraembryonic mesoderm and the yolk sac are derived from the hypoblast.
The trophoblast is the layer of cells that surrounds the blastocyst. During week 2, the trophoblast divides into two layers, the cytotrophoblast and the syncytiotrophoblast. They form the embryonic component of the placenta.
Cytotrophoblast: the inner layer; mitotically active
- Function: cells migrate outward and fuse to become the syncytiotrophoblast
Syncytiotrophoblast: the outer layer; mitotically inactive
Function: invades the endometrium to create lacunae (spaces that fill with maternal blood)
- Secretes beta-hCG to maintain the corpus luteum and the decidua (starts when implantation of the blastocyst occurs)
- Invades the endometrium to create lacunae (spaces that fill with maternal blood)
- Proteolytic enzymes secreted by the syncytiotrophoblast break down the extracellular matrix
- Formation of vacuoles within the syncytium, fusion of vacuoles to form lacunae (lacunar stage)
- Invasion of syncytiotrophoblast into maternal capillaries (sinusoids)
- Maternal sinusoids and lacunae fuse; maternal blood flows through the trophoblast → uteroplacental circulation
- Function: invades the endometrium to create lacunae (spaces that fill with maternal blood)
Formation of the chorionic cavity
- Starting point: The amniotic cavity and primary yolk sac are surrounded by trophoblast cells.
- Sequence of events
- The trophoblast grows significantly faster than the surrounding structures → a gap forms between it and the amniotic cavity.
- The gap is lined by the extraembryonic mesoderm.
- Renewed gap formation in the extraembryonic mesoderm results in the formation of a new cavity
- The extraembryonic mesoderm splits into two layers (somatopleuric and splanchnopleuric mesoderm) but remains attached at a connecting stalk
- Somatopleuric (parietal) mesoderm: lines the trophoblast
- Splanchnopleuric (visceral) mesoderm: surrounds the amniotic cavity and yolk sac with an intermediate germinal disc
Extraembryonic coelom (chorionic cavity)
- Cavity that is formed between the somatopleuric and splanchnopleuric layers → precursor of the gestational sac
- Lined by the chorion (outermost cell layer surrounding the embryo)
- Connecting stalk
Gastrulation is the formation of the trilaminar embryonic disc or gastrula through the migration of epiblast cells. Epiblast cells migrate through the primitive streak between the epiblast and hypoblast layers and form an intermediate cell layer called the intraembryonic mesoderm. The hypoblast is replaced by epiblast cells, from which the endoderm arises. The original epiblast becomes the ectoderm.
- Origin: primitive streak, an elongated accumulation of epiblasts
- Result: formation of the trilaminar embryonic disc (mesoderm, endoderm, and ectoderm)
Process: occurs weeks 3–4
- Mesoderm development (intraembryonic mesoderm)
- Endoderm development
- Ectoderm development: differentiation of remaining epiblast cells into ectoderm after migration of cells for endoderm, mesoderm, and notochord
All embryonic tissue originates from the epiblast!
- Definition: : development of the notochord, a rodlike structure between the ectoderm and endoderm that is essential for the development of the nervous system and primitive skeletal structures
- Location: The notochord migrates along the primitive streak (the future craniocaudal axis), and ends at the prechordal plate. It is part of the axial mesoderm
- Process: occurs weeks 3–4 (at the same time as development of the trilaminar embryonic disc)
- Derivatives: The nucleus pulposi of the intervertebral discs are remnants of the notochord.
Neurulation is the formation of the neural tube and neural crests, which are the precursors to the central and peripheral nervous systems. During this process, the surface ectoderm is also formed, which gives rise to the epidermis.
- Definition: formation of the neural tube and neural crests via neural plate folding
- The central area of the neural plate decreases (invagination) and becomes the neural groove.
- The neural folds are found on both longitudinal sides of the neural groove.
- The neural folds converge (week 3) and convert the neural groove into the neural tube.
- The neural tube communicates with the amniotic cavity through cranial and caudal openings (neuropore).
- Fusion of the opposite sides of the neural folds results in the formation of the surface ectoderm.
- Neural fold fusion leads to several cells dissociating from the epithelial cluster, which deposit between the neural tube and surface ectoderm as the neural crest cells.
The entire nervous system develops from the ectoderm!
Definition: An embryological structure with five paired arches composed of mesodermal and neural crest cells bound externally by an ectodermal cleft and internally by an endodermal pouch, which differentiate into various head and neck structures. The branchial apparatus is externally visible below the developing brain of a 4-week-old embryo. The fifth arch regresses in utero and does not contribute to the development of any head and neck structures.
- Pharyngeal arch: the central mesenchymal core, which contains a nerve, an artery, and cartilage
- Pharyngeal pouch: endodermal origin
- Pharyngeal groove: ectodermal origin
|Pharyngeal arch derivatives|
|Pharyngeal arch||Nerve||Artery||Muscle||Skeletal structure|
First pharyngeal arch
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Second pharyngeal arch
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Third pharyngeal arch
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Fourth pharyngeal arch
|Sixth pharyngeal arch|| |
The inferior parathyroid glands arise cranially (3rd pouch) but end up caudally (lower poles of the thyroid gland). The superior parathyroid glands arise caudally (4th pouch) but end up cranially (superior poles of the thyroid gland).
- The first pharyngeal groove develops into the external auditory meatus, the auditory canal, and the external aspect of the tympanic membrane.
- The second to fourth pharyngeal grooves are obliterated in-utero by the rapid growth of the second pharyngeal arch, and they do not differentiate into any of the head and neck structures.
- The second pharyngeal arch develops faster than the others → overlap and merge with the second and third arches → grooves lose their connection with the amnion → cervical sinus is formed.
- The cervical sinus is obliterated during later development.
- Failure of the cervical sinus to obliterate completely results in , which can lead to lateral cervical fistula.
A lateral cervical fistula is prone to infection and is a clear indication for operative treatment!
The aortic arches are blood vessels that run in between the pharyngeal pouches and form the major head and neck arteries. The arches develop in craniocaudal order, with the first two arches obliterating early and the fifth either never developing or also obliterating without giving rise to a vessel.
Morphogenesis is the process by which the shape of an organism is generated. The embryo undergoes folding, resulting in transformation of the flat, germinal disc into an embryo that approaches the human form during the course of the pregnancy. During the folding processes, the abdominal cavity, the abdominal wall, and the gut tube are formed. At the cranial and caudal embryonic poles, there is an area devoid of the mesoderm where the endoderm and ectoderm come into direct contact with one another, called the buccopharyngeal or cloacal membrane. The mouth and anus will later form in these areas.
Body axis determination
- Dorsoventral body axis: formed as the bilaminar disc develops
Craniocaudal body axis: formed by the extension of the primitive streak
- Cranial pole: primitive nodes
- Right-left differentiation: The positioning of unpaired chest and abdominal organs is determined by asymmetric expression of signaling molecules in the lateral plate mesoderm.
Situs inversus is a very rare congenital condition in which the chest and abdominal organs are reversed or mirrored. It is usually considered a benign condition, but can also present as part of a syndrome, e.g., Kartagener syndrome.
- Process: The cranial and caudal embryonic poles curl, resulting in curving of the germinal disc.
- The embryo develops a C form.
- Caudal end: tail fold
- Cranial end: head fold
- Constriction of the yolk sac
- The embryo develops a C form.
- Ventral outgrowth of the lateral margins of the germinal disc
- The ectoderm and the overlying lateral plate mesoderm on both sides converge.
- Adhesion of both sides results in the formation of a lateral and anterior body wall as well as a cavity, the blastocoel (intraembryonic coelom).
- The endoderm and the overlying lateral plate mesoderm on both sides converge → gut tube formation
The midgut stays connected to yolk sac remnants via the vitelline duct (omphalomesenteric duct). This duct is obliterated during the course of embryogenesis. Persistence of this duct most commonly results in Meckel diverticulum but could also cause retroumbilical cysts and fistulae.
Buccopharyngeal and cloacal membrane formation
- Buccopharyngeal membrane: region without mesoderm at the cranial embryonic pole
- Cloacal membrane: region without mesoderm at the caudal embryonic pole
- Formation of future body orifices
- The embryo is connected to its external environment (e.g., amniotic fluid) via the body orifices.
Abnormalities of morphogenesis
|Agenesis|| || |
|Aplasia|| || |
|Hypoplasia|| || |
|Disruption|| || |
|Deformation|| || |
|Malformation|| || || |
|Syndrome|| || |
Differentiation of the mesoderm
- Location: tube-shaped area of the mesoderm surrounding the notochord
- Components: somites
- The paraxial mesoderm becomes divided into segmented round cell clusters (somites) along the neural tube.
- Up to the beginning of the week 5, an initial 42–44 somite pairs are formed in a craniocaudal direction.
- Degeneration of several somite pairs, resulting in a remaining 35–37 somite pairs.
- As primitive segments, somites determine body segmentation
- Sclerotome: medial migration of cells toward the notochord and fusion of both sclerotomes of a somite pair
- Dermatome: migration toward the surface ectoderm
- Myotome: subdivision into the dorsal epimere and ventral hypomere skeletal muscles in the lateral and anterior regions of the thorax and abdomen
- Somite segments
- Location: lateral to the paraxial mesoderm
- Components: urogenital fold, consisting of the nephrogenic ridge and genital ridge
- Location: lateral to the intermediate mesoderm
Sequence of events
- In the second week of development, small folds develop in lateral aspect of the mesoderm.
- These folds split horizontally to form two components.
- The space between these components is called the coelom
- The two coeloms from either side fuse at the end of the lateral folding of the embryo to form one large cavity, the intraembryonic coelom, which will differentiate into the thoracic and abdominal cavities (see “morphogenesis” above).
Mesenchyme ≠ mesoderm: The mesoderm is one of the three germinal layers that differentiates into different tissues. The mesenchyme is embryonic connective tissue that develops from the mesoderm and other germ layers.
A fate map is used to determine the origin of a cell lineage, e.g., a germ layer. The following table provides an overview of the various tissue types and structures that arise from the three germ layers.
|Germ layer structure||Differentiated tissue/organs|
Neuroectoderm (neural tube)
|Neural crest|| |
|Surface ectodermal placodes|
|Mesoderm (intraembryonic mesoderm)||Axial||Prechordal|| |
|Lateral plate mesoderm||Splanchnopleuric mesoderm|