CNS Development

I. Neurulation

• Neurulation: The process of neural fold formation, elevation, and closure to form the neural tube.   - Timeline: Begins at the 3rd week of development and continues until Day 28 (4th week of gestation).

Table 1. Germ Cell Differentiation (Day 17) and their derivatives:

  - Germ Layers:     - Ectoderm: Forms CNS, PNS.     - Mesoderm: Forms the vascular system, muscle, connective tissue.     - Endoderm: Forms gastrointestinal tract, liver, lungs.

• CNS development starts with the appearance of:   - Notochord: Located inferiorly.   - Neural Plate: Located superiorly.

Figure 1: Day 17 of Neurulation

   - Source: Marieb, 9th Ed.

• Neurulation Progress:   - End of 3rd week: Elevation of lateral edges of the neural plate forms neural folds.     - Neural Groove: Depressed midline region between lateral neural folds.     - Elevated neural folds approach each other and fuse to form the neural tube.

Figure 2: Day 19 of Neurulation

   - Source: Marieb, 5th Ed.

• Fusion Process:   - Begins in the cervical region at the level of the 5th somite.   - Proceeds cephalad (cranially) and caudad (caudally).   - Open Ends:     - Anterior Neuropore: Cranial side.     - Posterior Neuropore: Caudal side.

• Closing of Neuropores:   - Marks the end of neurulation.   - Anterior neuropore closes first (Day 24-25), followed by the posterior neuropore (Day 27-28).

• After closure, the CNS appears as a T-shaped tubular structure:   - Narrow caudal portion forms the spinal cord.   - Broader cephalic portion contains brain vesicles.

Table 2: Neurospores and their day of closure

• Neural Crest Cells:   - Formed at the tip of neural folds.   - Leave lateral border of the neuroectoderm to enter the underlying mesoderm.

Figure 4: Neural Crest Cell Pathways

   - Source: Langman, 12th Ed.

Table 3: Neural Crest Derivatives

• Neural Crest Derivatives:   - Connective tissue and bones of the face and skull.   - Cranial nerve ganglia, C cells of the thyroid gland.   - Spinal (dorsal root) ganglia, sympathetic chain, adrenal medulla, Schwann cells, glial cells.   - Melanocytes, smooth muscle cells.

II. Development of the Spinal Cord

A. Neural Tube

• A narrow channel that folds and closes during the 3rd and 4th weeks of pregnancy, leading to the formation of the brain and spinal cord.

Table 4: Layers of the Neural Tube

• Layers:   - Ependymal/Ventricular Layer (Neuroepithelium): Formed from the proliferation of neuroepithelial cells.   - Mantle Layer (Intermediate Zone): Contains neuroblasts leading to gray matter of the spinal cord.   - Marginal Layer: Outermost layer containing myelinated nerve fibers, appears as white matter.

B. Histologic Differentiation

Neuroblasts

• Primitive nerve cells that arise from neuroepithelial cells.   - Initial structure: Transient dendrite with a central process extending into the lumen, which disappears upon migration to the mantle layer.   - Types of Neuroblasts:     - Apolar Neuroblast: Round, lacks cytoplasmic processes.     - Bipolar Neuroblast: Forms primitive axon and dendrite extending outwards.     - Multipolar Neuroblast: Gives rise to adult nerve cells.

Table 5: Differentiation of Neuroblasts

Glioblasts

• Derived from neuroepithelial cells.   - Migrate to mantle and marginal layers to differentiate into astrocytes and oligodendroglia.

Table 6: Glioblast Differentiation

Ependymal Cells

• Derived from neuroepithelial cells remaining after formation of neuroblasts and glioblasts.
• Line the ventricles of the brain and the central canal of the spinal cord.

Microglia

• Derived from vascular mesenchyme.
• Function as phagocytic cells in the nervous system.

Neural Tube Development Details

• Identifiable ventral (Basal Plate) and dorsal (Alar Plate) thickenings in the spinal cord:   - Basal Plate: Ventral motor horn cells; forms motor areas of spinal cord.   - Alar Plate: Dorsal horn; forms sensory areas.

Figure 10: Development of Neural Tube

   - Source: Langman, 12th Ed.

• Position of the Cord and Nervous System Development:   - By the 3rd month of development, the spinal cord extends the entire length of the embryo.   - Birth: Spinal cord ends at L2-L3 level; in adults at L1-L2.   - Results in oblique positioning of spinal nerves from their segment of origin in the spinal cord through their associated vertebral levels.

Spinal Nerve Development

• Absence of neurons in the basal plate breaks through the marginal zone to become the ventral motor root.
• Neuroblasts from the alar plate form sensory processes that contribute to spinal nerve formation.   - Processes include centrally and peripherally growing processes leading to dorsal sensory root formation.

Myelination

• Begins during the 4th month; myelin deposition changes nerve fibers appearance to white.

Table 7: Schwann Cell vs Oligodendroglial Cell

III. Development of the Brain Vesicles

A. Primary Brain Vesicles

• Day 27 marks the formation of three primary brain vesicles:   - Prosencephalon (Forebrain).   - Mesencephalon (Midbrain) - remains intact, does not divide.   - Rhombencephalon (Hindbrain) - divides into:     - Metencephalon: Develops into pons and cerebellum.     - Myelencephalon: Develops into medulla oblongata.

Figure 16: Primary Brain Vesicle

   - Source: Netter's Atlas of Neuroscience, 4th Ed.

B. Secondary Brain Vesicles (by the end of the 5th week)

• Each primary brain vesicle gives rise to secondary structures:
• Table 8: Brain Ventricles and Structures

A. Brainstem

• Divided into basal and alar plates reflecting motor and sensory areas, respectively.

B. Higher Centers

• Involves accentuation of alar plates and regression of basal plates.
• Rhombencephalon organization into:   - Myelencephalon and Metencephalon.

Figure 20: Myelencephalon Parts and Development

   - Source: Lecturer’s PPT

V. Clinical Correlation

A. Neural Tube Defects

Spina Bifida

• Condition involving incomplete development of the vertebral arches, which may impact neural structures.
• Types of Spina Bifida:   - Spina Bifida Occulta: Covered vertebrae defects, normal neurologic findings.   - Spina Bifida Cystica: Meninges and/or neural tissues protruding through a defect.   - Table 11: Other Types of Spina Bifida:     - Spina bifida with meningocele: Only meninges protrude.     - Spina bifida with myelomeningocele: Neural tissue included - most severe.     - Spina bifida with myeloschisis: Neural tissue remains a flattened mass.

B. Cranial Defects

Holoprosencephaly

• Abnormalities due to loss of midline structures.
• Can result in lateral ventricles merging into a single telencephalic vesicle, leading to facial deformities.

Schizencephaly

• Rare disorder causing clefts in the cerebral hemispheres.
• Two types: Close (Type I) and Open (Type II).

Encephalocele

• Protrusions of the brain through skull openings due to neural tube failure to close.

Clinical Significance

• Importance of Folic Acid: Supplementation prior to conception and during pregnancy can prevent neural tube defects.

VI. Review Questions

1. At what week does neurulation typically begin?    - Answer: B. 3rd week of gestation.
2. What layer of the neural tube becomes the white matter?    - Answer: C. Marginal layer.
3. Which primary brain vesicle remains intact without further division?    - Answer: B. Mesencephalon.
4. What is the most severe type of spina bifida?    - Answer: A. Spina bifida with myelomeningocele.
5. Which germ layer forms the CNS?    - Answer: C. Ectoderm.

VII. References

• Moore, K., Dalley, A. & Agur, A. (2018). Clinical Anatomy (8th Ed.). Wolters Kluwer.
• Netter, F. H. (2018). Atlas of Human Anatomy (8th ed.). Saunders.
• Uy, Z.M.C. (2023). Development of the Central Nervous System.[Asynchronous Lecture].
• Uy, Z.M.C. (2026). Development of the Central Nervous.[Synchronous Lecture].

VIII. Appendix

• Organization of Alar and Basal Plate Neurons in the Brainstem.