EMBRYOLOGY OF THE CENTRAL NERVOUS SYSTEM

Mark Dias

Early embryonic development (1, 2, 6)

Figure 1: Early formation of the embryo. A. formation of inner cell mass and surrounding trophoblast; B. formation of epiblast, hypoblast and amnoinic sac; C. formation of prochordal plate (craniocaudal orientation)

Gastrulation

  1. PS elongates toward cranial end of embryo between POD 13-16
  2. Reaches its full length by POD 16, covering midline in caudal half of embryo
  3. PS begins to regress beyond POD 16 back toward the caudal embryo, ends up as caudal cell mass by POD 28
  4. During elongation, prospective endodermal cells move toward the midline and invaginate (ingress) through the cranial half of the primitive groove (extra-embryonic cells ingress through the caudal half), displacing hypoblast cells laterally and replacing them beneath epiblast to form definitive endoderm (giving rise to respiratory and gastrointestinal epithelium)
  5. During regression mesodermal cells ingress through primitive streak to form somitic (giving rise to somites), intermediate (giving rise to renal system) and somatopleural (giving rise to limbs) mesoderm on either side of the PS between epiblast and newly formed endoderm
  6. Remaining cells of epiblast spread out and differentiate to form neuroectoderm (central nervous system) and cutaneous ectoderm (skin)
  7. Gastrulation converts the embryo from a two layered structure having epiblast and hypoblast, to a three-layered structure containing ectoderm, mesoderm, and endoderm (figure 2a)
  1. During PS elongation endoderm ingresses through the primitive pit
  2. During PS regression, prospective notochordal cells ingress through the primitive pit, between the newly formed endoderm and neuroectoderm in the midline to form the notochordal canal (figure 2b)
  1. Notochordal canal fuses (figure 3b) with underlying endoderm (intercalation) for approximately 3 days, during which amnion is contiguous, via the lumen of the notochordal canal, with the yolk sac; this communication is called the primitive neurenteric canal.
  2. By POD 25 the notochordal process has reformed, separating from the endoderm (excalation), and becoming the true notochord, and the primitive neurenteric canal is obliterated (figure 3c)
Figure 2: Gastrulation. A. ingression of epiblast cells through primitive groove during primitive streak regression become prospective endodermal and mesodermal cells. B. ingression of epiblast cells from Hensen’s node into primitive pit produces prospective notochordal cells.

Figure 3: Intercalation and excalation of notochordal process: A. the notochordal canal exists as a tube of cells radially arranged about a central lumen, situated between the dorsal ectoderm and the ventral endoderm. B. fusion of the cells of the notochordal process with the underlying endoderm creates the primitive neurenteric canal (PNC) and temporarily communicating the amnionic and yolk sacs. C. the notochordal process excalates from the endoderm, recreating the notochord and eliminating the PNC.

Primary Neurulation (1, 2, 6, 10)

  1. Formation of a midline furrow, the neural groove (or median hingepoint) directly overlying the notochord (and induced by the notochord)
  2. Elevation of the laterally paired neural folds surrounding the neural groove
  3. Formation of bilaterally paired lateral hingepoints and convergence of the neural folds toward the midline
  4. Fusion of the neural folds to one another, and separation of the cutaneous from neuroectoderm (dysjunction)
  1. Branchial arch derivatives
  2. Dorsal roots and dorsal root ganglia
  3. Autonomic ganglia (both sympathetic and parasympathetic)
  4. Adrenal medulla (adrenergic cells)
Figure 4: Primary neurulation: A. neural plate stage; B. midline bending of the neural plate over the notochord to form the neural folds; C. lateral bending with convergence of the neural folds; D. neural fold fusion with dysjunction of the overlying ectoderm. From Gilbert, Developmental Biology (7th Edition), Sinauer Assoc, Sunderland MA (2003), p. 394

Secondary Neurulation (2, 8, 9)

Figure 5: Secondary neurulation. Upper portion illustrates secondary neurulation in chick embryos in which small tubules form (A) from the caudal cell mass (CCM) caudal to the neural tube formed from primary neurulation (1o NT) (A), coalesce (B) to form the secondary neural tube (2 o NT) (B), and eventually fuse with the neural tube formed by primary neurulation (1o NT); (C). Lower portion illustrates mouse secondary neurulation in which the secondary neural tube (2 o NT) grows by addition of cells to the 1o NT from the caudal cell mass (CCM). NC: notochord

Ascent of the Conus Medullaris (3, 11)

Formation of Primary and Secondary Neural Vesicles and Flexures (4, 6, 7)

Development of Alar and Basal Plates; Formation of Cranial Nerve Nuclei (4, 5)

Neuronal Migration - Formation of the Spinal Cord, Brainstem, Cerebellum, Deep Nuclei and Cortex (5)

  1. Cells in the ependymal zone migrate to form the marginal later (layer I) of the cortex
  2. A subventricular (germinal matrix) zone develops immediately adjacent to the ventricular ependyma
  3. Cells from the germinal matrix migrate to the cortex in an inside out pattern with layer 6 neurons forming first and successive waves of migration forming more superficial layers
  4. Locally multiplying presumably glial cells populate the cortex
  5. Remaining non-migrating germinal matrix produces ependymal cells.

Suggested Reading

Dias MS, and McLone DG: Normal and Abnormal Embryology of the Nervous System. In McLone (editor), Pediatric Neurosurgery: Neurosurgery of the Developing Nervous System (Fourth Edition). WB Saunders Co. Philadelphia, 2001

References

  1. Dias M, S., Schoenwolf GC: Molecular biology of early neural development, in McLone DG (ed): Pediatric Neurosurgery: Surgery of the Developing Nervous System. Philadelphia, W.B. Saunders, 2001, pp 73-86.
  2. Dias MS, McLone DG: Normal and abnormal early development of the nervous system, in McLone DG (ed): Pediatric Neurosurgery: Surgery of the Developing Nervous System. Philadelphia, W.B. Saunders, 2001, pp 31-71.
  3. Kunimoto K: The development and reduction of the tail and of the caudal end of the spinal cord. Contrib Embryol 8:161-198, 1918.
  4. Moore KL: The Developing Human: clinically oriented embryology. Philadelphia, W.B. Saunders Co., 1982.
  5. Norman MG, McGillivray BC, Kalousek DK, Hill A, Poskitt KJ: Embryology of the central nervous system, in Norman MG, McGillivary BC, Kalousek DK, Hill A, Poskitt KJ (eds): Congenital Malformations of the Brain: Pathological, Embryological, Clinical, Radiological, and Genetic Aspects. New York, Oxford University Press, 1995, pp 9-51.
  6. O’Rahilly R, Müller F: Developmental Stages in Human Embryos. Washington, Carnegie Institution of Washington, 1987.
  7. O’Rahilly R, Müller F: The Embryonic Human Brain. An Atlas of Developmental Stages. New York, Wiley-Liss, 1994.
  8. Schoenwolf GC: Histological and ultrastructural studies of secondary neurulation in mouse embryos. Am J Anat 169:361-376, 1984.
  9. Schoenwolf GC, DeLongo J: Ultrastructure of secondary neurulation in the chick embryo. Am J Anat 158:43-63, 1980. 1
  10. Schoenwolf GC, Smith JL: Mechanisms of neurulation: traditional viewpoint and recent advances. Development 109:243-270, 1990.
  11. Streeter GL: Factors involved in the formation of the filum terminale. Am J Anat 25:1-11, 1919.