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Last updated: August 10, 2020


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.


First week of embryonic development (days 1–7)

See stages of pregnancy.

Second week of embryonic development (days 8–14)

3rd and 4th week of embryonic development (days 15–28)

The embryo is extremely susceptible to teratogens from week 3 to week 8, when the process of organogenesis occurs.

Fifth to eighth 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 5
  • Rapid head growth through development of the brain and facial structures
  • The mesonephros, which is formed between weeks 3 and 5, bulges in the urogenital ridge.
  • Development and differentiation of additional pharyngeal arches
Week 6
  • Digital ray development
  • Auricular hillock development, which later becomes the auricle
  • Eye is clearly recognizable through retinal pigment development
  • Back starts to straighten
  • Formation of a physiological umbilical hernia
  • Fetal heart beats are visible on transvaginal ultrasound.
Week 7
  • The proximal bones of the upper limbs start to ossify.
Week 8
  • Recognizable human form
  • Fingers are initially separated from one another by skin flaps, followed by complete separation.
  • The proximal bones of the lower limbs start to ossify.
  • Genitals have sex-specific characteristics; however, these are not yet sufficient to determine sex on ultrasound.
  • Fetal movements begin.

Embryoblast and trophoblast development


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.

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 bilaminar disc forms the dividing layer between the yolk sac and amniotic cavity.


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.

The extraembryonic coelom is also called the chorionic cavity, which is lined by the chorion.



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.

All embryonic tissue originates from the epiblast!



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.

The entire nervous system develops from the ectoderm!

Neural tube defects are one of the most common CNS malformations and develop as a result of incomplete closure of the neural tube (e.g., spina bifida, anencephaly).

Branchial apparatus

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 arches

Pharyngeal arch derivatives
Pharyngeal arch Nerve Artery Muscle Skeletal structure

First pharyngeal arch

(mandibular arch)

Second pharyngeal arch

(hyoid arch)

  • Obliterates completely

Third pharyngeal arch

  • Hyoid bones: greater horn and body

Fourth pharyngeal arch

Sixth pharyngeal arch

Pharyngeal pouch

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).

Pharyngeal grooves

  • Derivatives
  • Cervical sinus
    • 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 branchial cleft sinus, which can lead to lateral cervical fistula.

A lateral cervical fistula is prone to infection and is a clear indication for operative treatment!

Aortic arches

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.

Aortic arches Derivatives
  • Maxillary artery: remnant of obliterated first arch
  • Most parts of the second aortic arch obliterate early
    • Hyoid artery: remnant of the largely obliterated second arch
    • Stapedial artery: transient branch of the hyoid artery (typically regresses around week 10 of development)

1st is maximal (maxillary artery); Second for Stapedial; C is the 3rd letter of the alphabet (Common Carotid, proximal internal Carotid); 4th arch and 4 limbs (systemic arch).


Morphogenesis is the process by which the shape of an organism is generated. The embryo undergoes folding, resulting in transformation of the flat, embryonic 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

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.

Craniocaudal folding

  • Process: The cranial and caudal embryonic poles curl, resulting in curving of the embryonic disc.
  • Result:
    • The embryo develops a C form.
    • Constriction of the yolk sac

Lateral folding

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

Abnormalities of morphogenesis

Process Definition Characteristics Example
  • The organ is not present.
  • Primordial tissue from which the organ is derived is absent.
  • The organ is not present.
  • Primordial tissue from which the organ is derived is present.
  • Underdevelopment of an organ
  • Primordial tissue from which the organ is derived is present.
  • Breakdown of a previously normal structure or tissue
  • Amniotic band syndrome
    • Entrapment of fetal parts in fibrous amniotic bands
    • Clinical features
      • Constriction rings or bands
      • Autoamputation of digits or limbs
      • Syndactyly
      • Abdominal wall defects, visceral protrusions
      • Craniofacial anomalies
  • Interruption of the normal development of an organ due to an extrinsic force (e.g., in case of multiple gestations or big leiomyomas)
  • Occurs after week 8
  • Interruption of the normal development of an organ due to an intrinsic process
  • Occurs between week 3 and week 8
  • A single event that causes multiple abnormalities
  • A set of clinical features that consistently occur together
  • Commonly caused by genetic mutations (e.g., trisomy 21)


Differentiation of the germinal disc

Differentiation of the mesoderm

Axial mesoderm

Paraxial mesoderm

Intermediate mesoderm

Lateral plate mesoderm

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.

Fate mapping

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
Surface ectoderm
Mesoderm (intraembryonic mesoderm) Axial Prechordal
Paraxial Sclerotome
Lateral plate mesoderm Splanchnic (splanchnopleuric) mesoderm
Somatic (somatopleuric) mesoderm



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  2. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education ; 2017
  3. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. McGraw-Hill Medical ; 2017
  4. Kadian YS, Verma A, Rattan KN, Kajal P. Vitellointestinal duct anomalies in infancy. J Neonatal Surg. 2016; 5 (3): p.30. doi: 10.21699/jns.v5i3.351 . | Open in Read by QxMD
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