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Embryogenesis

Last updated: March 8, 2021

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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.

Embryonic development

This table is based on time since fertilization (i.e., developmental age), instead of time since first day of last menstrual period (i.e., gestational age).

Overview
Day/week Characteristics Possible disorders
Day 0
  • Capacitation: maturation of the sperm in the female genital tract
  • Fertilization (conception): usually occurs in the fallopian tubes (most commonly in the ampulla) within 1 day of ovulation
  • Conjugation (conception): fusion of the sperm and ovum to form the zygote (single cell)
Day 1–5
Day 6
Days 6–14
Weeks 3–4
  • Embryopathies: complex anomalies of individual organs during a time when the developing embryo is particularly susceptible to injury
  • Etiology
Week 5
  • Weeks 5–8 of embryogenesis mainly involves organogenesis.
    • 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
Week 7
  • The proximal bones of the upper limbs start to ossify.

Week 8
  • Organogenesis is complete by the end of 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.
  • Fetal movements begin.
Week 9–12
  • Fetogenesis: the fetus matures and grows
  • Genitals have sex-specific characteristics; sex can be determined on ultrasound at week 12.

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

The developmental events from week 2 to week 4 can be remembered as follows: At 2 weeks there are 2 layers (bilaminar disc), 3 weeks there are 3 layers (trilaminar disc) and 4 weeks there are 4 limb buds and 4 heart chambers present.

Embryoblast

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.

Trophoblast

Cytotrophoblast

Cytotrophobasts make “cytos” (cells); Syncytotrophoblasts synthesize hormones.

Syncytiotrophoblast

Formation of the chorionic cavity

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).

Neural crest derivatives (Cranial bones, Adrenal medulla, Leptomeninges, Melanocytes, Enterochromaffin cells, Tracheal cartilage, PNS ganglia, Odontoblasts, Spiral membrane, and Endocardial cushions): Embryos have CALMEST POSE.

The brachial apparatus is 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.

Derivatives from the outer to the inner layer (Groove: ectoderm; Arch: mesoderm and neural crest; Pouch: endoderm): GAP

Pharyngeal arches

Pharyngeal arch derivatives
Pharyngeal arches (the fifth pharyngeal arch only exists transiently in human embryos) Nerves (innervate the structures derived from the arches; do not originate from them) Arteries Muscles Skeletal structures Related pathologies

First pharyngeal arch

(mandibular arch)

Second pharyngeal arch

(hyoid arch)

  • Obliterates completely

Third pharyngeal arch

  • Hyoid bones: greater horn and body
  • N/A

Fourth pharyngeal arch

  • N/A
Sixth pharyngeal arch
  • N/A

Sensory and motor nerves do not derive from pharyngeal arches, but from the neural crest and neuroectoderm respectively.

Pharyngeal pouch

The inferior parathyroid glands arise cranially (3rd pouch) but migrate caudally (lower poles of the thyroid gland). The superior parathyroid glands arise caudally (4th pouch) but migrate cranially (superior poles of the thyroid gland).

Pharyngeal grooves

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.

Overview of development of aortic arches
Aortic arches Derivatives
First
  • Maxillary artery: remnant of obliterated first arch
Second
  • 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)
Third
Fourth
Sixth

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 [1]

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

Process

Results

  • Formation of future body orifices
  • The embryo is connected to its external environment (e.g., amniotic fluid) via the body orifices.

Abnormalities of morphogenesis

Overview
Process Definition Characteristics Example
Agenesis
  • The organ is not present.
  • Primordial tissue from which the organ is derived is absent.
Aplasia
  • The organ is not present.
  • Primordial tissue from which the organ is derived is present.
Hypoplasia
  • Underdevelopment of an organ
  • Primordial tissue from which the organ is derived is present.
Disruption
  • Breakdown of a previously normal structure or tissue
  • N/A
  • 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
Deformation
  • 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
Malformation
  • Interruption of the normal development of an organ due to an intrinsic process
  • Occurs between week 3 and week 8
Sequence
  • A single event that causes multiple abnormalities
  • N/A
Syndrome
  • A set of clinical features that consistently occur together
  • Commonly caused by genetic mutations (e.g., trisomy 21)
Field defect
  • N/A

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.

Overview
Germ layer Germ layer structures Differentiated tissue/organs
Ectoderm
  • Surface ectodermal placodes
Mesoderm (intraembryonic mesoderm)
  • Axial
  • Prechordal
  • Paraxial
  • Myotome
  • Intermediate
Endoderm

Ectoderm: ec-sternal layer; Mesoderm: middle layer; Endoderm: en-ternal layer.

  1. 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
  2. Sadler TW. Langman's Medical Embryology. Lippincott Williams & Wilkins ; 2011