Central nervous system (CNS) embryology is a broad subject. This article serves as a summary of CNS organogenesis as well as a review the framework of embryology, the embryogenesis of the brain and spinal cord, various tests that can be performed in utero to test for CNS anomalies, and problems that may be encountered during embryogenesis, with particular attention to the CNS.
The CNS system involves 3 germinal layers: ectoderm, mesoderm, and endoderm.
The endoderm gives rise to the lining of the gastrointestinal and respiratory systems. It also gives rise to abdominal organs such as the liver, pancreas, and bladder.
The mesoderm is differentiated into 3 parts:
Embryological Transformations
Because these changes do not occur at once, embryology is a complicated subject. The following timing of embryological developments, with particular attention to the CNS, offers a greater understanding of the process.
Thirty-five to 38 weeks (37 to 40 gestational age): Baby now has a firm grasp with hands. Testes may have descended in males.[1][2]
Embryogenesis: Weeks 2 to 8
Beginning with the trilaminar germ disc, which refers to the epiblast and hypoblast, the epiblast cells undergo an epithelial-mesenchymal transition that replaces the hypoblast. They also proliferate in the middle layer to form the mesoderm where it will remain mesenchymal to form connective tissue. The primitive streak then starts to appear superiorly from the thickened region of ectoderm. It grows caudal to cranial and induces the notochord formation. The ectoderm then invaginates as cells migrate to form the primitive node and primitive pit where the notochordal process is formed.
The CNS is derived from the neuroectoderm: notochord induces the formation of the neural plate (thickening of the ectodermal layer), which further differentiates to form neural folds with a neural groove in between, leading to the formation of the neural tube (via neurulation).
Spinal Cord
The spinal cord is formed from the neural plate, now contains 3 layers:[3][4][3]
While this article summarizes the embryological changes that occur within the CNS, the peripheral nervous system (PNS) is formed from neuroepithelial cells. These cells travel from the pia mater to the ventricular layer of the spinal cord, where they differentiate and migrate to form glioblasts (for example, support cells, Schwann cells), neurons, and ependymal cells. As this information is often tested on boards, that myelin sheath, a sheath composed of support cells, wraps around axons and insulate neurons to increase the speed of neuronal conduction.
Three membranous layers cover the whole CNS:
Brain
During brain formation, there are 3 primary brain vesicles that differentiate into 5 secondary brain vesicles. See image.
Finally, the hypophysis gives rise to the pituitary gland, which has 2 origins. The posterior pituitary is an outgrowth of the hypothalamus, and, therefore, has a direct connection. On the other hand, the anterior pituitary is an ectodermal growth from the mouth. It depends on a dense capillary network and communicates with the brain via the vascular system.[5][6]
Although beyond the scope of this article, there is also a Quad-screen test which can be performed in the second trimester. The components of this screening test include AFP, hCG, Estriol, and Inhibin-A.[7]
Embryogenesis can be complicated and result in mild or extreme defects (pathophysiological changes).
Dysraphism in the cranium causes malformations analogous to spina bifida[8]:
Pathophysiological processes that can occur during embryogenesis are rare and do not occur very often, and when they do, the newborn is alive and not stillborn. However, the newborn may require certain surgeries to correct the craniofacial anomalies before significant damage occurs.[9] Furthermore, those babies born with spina bifida require further evaluation with ultrasound and surgical correction of the spinal cord to prevent herniation or other complications.
Clinically speaking, to avoid the abnormal embryological development, the mother should abstain from teratogens or any external factor that can influence the growth of the baby, especially during weeks 3 through 8 of the embryogenesis. Significant teratogens include alcohol, tobacco use, certain prescription drugs, and illicit drugs. Most importantly, women seeking to get pregnant or who are pregnant take multivitamins, especially folic acid supplements to aid with neurodevelopment.[10]
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[3] | Gouti M,Metzis V,Briscoe J, The route to spinal cord cell types: a tale of signals and switches. Trends in genetics : TIG. 2015 Jun [PubMed PMID: 25823696] |
[4] | Kaplan KM,Spivak JM,Bendo JA, Embryology of the spine and associated congenital abnormalities. The spine journal : official journal of the North American Spine Society. 2005 Sep-Oct [PubMed PMID: 16153587] |
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[7] | Dorney E,Black KI, Preconception care. Australian journal of general practice. 2018 Jul [PubMed PMID: 30114868] |
[8] | Shamji MF,Ibrahim A, IMAGES IN CLINICAL MEDICINE. Cervical Meningocele. The New England journal of medicine. 2015 Jul 23 [PubMed PMID: 26200992] |
[9] | Zakhary GM,Montes DM,Woerner JE,Notarianni C,Ghali GE, Surgical correction of craniosynostosis. A review of 100 cases. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2014 Dec [PubMed PMID: 24969768] |
[10] | van Gelder MM,de Jong-van den Berg LT,Roeleveld N, Drugs associated with teratogenic mechanisms. Part II: a literature review of the evidence on human risks. Human reproduction (Oxford, England). 2014 Jan [PubMed PMID: 24108217] |