Embryological Development of the Central Nervous System

Question 1

Describe neurulation:

Answer 1

Neurulation - process during embryonic development in which the neural tube forms, eventually giving rise to the central nervous system (brain and spinal cord). It occurs in three main steps:

Formation of the neural plate:
Ectodermal cells above the notochord thicken to form the neural plate.

Shaping and folding:
The edges of the neural plate elevate, forming neural folds, while the center forms the neural groove.

Closure of the neural tube:
The neural folds converge and fuse at the midline, forming the neural tube. This begins in the cervical region and progresses cranially and caudally.

Question 2

What is the role of the notochord ?

Answer 2

The notochord is a mesodermal structure that acts as a key signaling center during neurulation.
It secretes signaling molecules like Sonic Hedgehog (Shh), which induce the overlying ectoderm to differentiate into the neural plate
The notochord also helps guide the folding and fusion of the neural plate into the neural tube.
After neurulation, the notochord contributes to the formation of the nucleus pulposus of intervertebral discs.

Question 3

Discuss the primary and secondary brain vesicles and explain what they develop into in the adult brain.

Answer 3

Primary Brain Vesicles (3-4 weeks of embryonic development)
- Prosencephalon (forebrain)
- Mesencephalon (midbrain)
- Rhombencephalon
(hindbrain)

The primary vesicles further differentiate into five secondary vesicles:

Prosencephalon splits into:
Telencephalon → Becomes the cerebrum (cerebral cortex, basal ganglia, limbic system).

Diencephalon → Forms the thalamus, hypothalamus, epithalamus, and retina.

Mesencephalon remains undivided: Becomes the midbrain (part of the brainstem).

Rhombencephalon splits into:
Metencephalon → Develops into the pons and cerebellum.
Myelencephalon → Forms the medulla oblongata.

Question 4

Describe the key events of neurogenesis, including proliferation and migration

Answer 4

Neurogenesis is the process by which new neurones are generated during embryonic development and, to a lesser extent, in the adult brain

Proliferation:

• neural stem cells (NSCs) and progenitor cells in the ventricular zone of the neural tube divide to produce neurones and glial cells
• symmetric division produces 2 identical stem cells expanding stem cell pool
• asymmetric division produces one neural progenitor cell and one differentiated cell
• controlled by signaling molecules like Notch and Wnt, and growth factors

Migration:

• new neurones migrate from their place of origin in the ventricular zone to their final destination in the brain
• radial migration involves neurones moving along radial glial fibres to form the layers of the cerebral cortex
• tangential migration involves neurones moving parallel to the brain’s surface
• migration is guided by chemical cues such as reelin and cell adhesion molecules (CAMs) to ensure correct positioning

Neuroblasts primarily migrate along the glia (glial mediate migration), but some will self propel via somal translocation

Question 5

Explain the development of the cerebral hemispheres

Answer 5

Early Development (Weeks 5–6):

• telencephalic vesicles expand bilaterally from the forebrain region
• rapid proliferation of neuroepithelial cells occurs in the walls of the telencephalon
• lateral ventricles form within each hemisphere

Expansion and Folding (Weeks 8–28):

• hemispheres grow disproportionately, particularly in the frontal, parietal, and temporal lobes, curving around the developing diencephalon
• hemispheres expand in a C-shaped pattern, which explains the curvature of the lateral ventricles
• corpus callosum forms, connecting the two hemispheres

Question 6

Describe gyri and sulci formation:

Answer 6

Initial Expansion:
Rapid proliferation of progenitor cells causes the telencephalon to expand disproportionately.

Formation of Gyri and Sulci:
Driven by differential growth rates in cortical regions.
Mechanical constraints (e.g., limited skull space) and signaling pathways (e.g., Fgf, Shh) contribute.
Increased surface area optimizes cognitive and neural processing capacity.

Maturation:
Gyri (ridges) and sulci (grooves) develop more prominently during the late fetal stage.
Primary sulci form first, followed by secondary and tertiary sulci.

Question 7

Describe neural tube defects:

Answer 7

Result from incomplete closure of the neural tube.

Examples:

Anencephaly: Failure of closure at the cranial end, leading to absent forebrain and skull.

Spina Bifida: Failure of closure at the caudal end, resulting in exposed spinal tissue.
Variants include spina bifida occulta, meningocele, and myelomeningocele.

Prevention: Adequate maternal folic acid intake during early pregnancy.

Question 8

Describe other Congenital Disorders:

Answer 8

Holoprosencephaly: Failure of prosencephalon division into
hemispheres.
Causes: Genetic mutations (e.g., SHH) or teratogens.

Microcephaly: Reduced brain size due to impaired proliferation or excessive apoptosis.
Associated with infections (e.g., Zika virus) and genetic factors.

Lissencephaly: “Smooth brain” caused by defective neuronal migration, leading to a lack of gyri/sulci.

Hydrocephalus: Excessive CSF accumulation, often due to obstruction of flow (e.g., aqueductal stenosis).