Development of Nervous System
1. INTRODUCTION AND OVERVIEW
The human nervous system develops from the Ectoderm starting in the 3rd week of gestation. It is the first organ system to initiate development and the last to complete it (myelination continues into adulthood).
- Inducer: The Notochord and Paraxial Mesoderm.
- Mechanism: Inhibition of BMP-4 allowing ectoderm to become neuroectoderm.
2. NEURULATION
Neurulation is the process of forming the neural tube from the neural plate. It occurs in two phases.
A. Primary Neurulation (Weeks 3-4)
Forms the brain and spinal cord down to the lumbar level.
- Neural Plate Formation (Day 18): Under the influence of the Notochord (secreting Noggin and Chordin), the dorsal ectoderm thickens to form the Neural Plate.
- Neural Groove (Day 20): The lateral edges of the plate elevate to form Neural Folds, creating a central depression called the Neural Groove.
- Neural Tube Formation: The folds approach each other in the midline and fuse.
- Fusion begins in the cervical region (5th somite) and proceeds cranially and caudally (like a zipper).
- The tube separates from the overlying surface ectoderm (which becomes skin).
B. Neuropore Closure (CRITICAL MILESTONES)
The open ends of the neural tube are called neuropores.
- Anterior (Cranial) Neuropore: Closes at Day 25 (18-20 somite stage). Failure -> Anencephaly.
- Posterior (Caudal) Neuropore: Closes at Day 27-28 (25 somite stage). Failure -> Spina Bifida.
C. Secondary Neurulation (Weeks 5-6)
Forms the sacral and coccygeal spinal cord.
- Caudal Cell Mass: A mesodermal structure at the tail end of the embryo.
- Canalization: The mass develops a hollow cavity which fuses with the primary neural tube.
- Retrogressive Differentiation: The tail gut regresses, leaving the Filum Terminale.
3. NEURAL CREST CELLS ("The 4th Germ Layer")
As the neural folds fuse, cells at the crest of the neuroectoderm detach and migrate laterally. They are multipotent.
| Derivative Group | Structures Formed |
|---|---|
| Ganglia | Dorsal root ganglia, Sympathetic chain, Parasympathetic ganglia, Cranial nerve ganglia |
| Cells | Schwann cells, Satellite cells, Melanocytes (skin), Chromaffin cells (adrenal medulla) |
| Head & Neck | Odontoblasts, Meninges (Pia/Arachnoid), Pharyngeal arch cartilages |
4. DEVELOPMENT OF THE SPINAL CORD
A. Histogenesis (Layers of the Tube)
The wall of the closed neural tube consists of neuroepithelial cells which differentiate into three concentric zones:
- Ventricular Zone (Inner): Ependymal layer; source of all neurons and macroglia.
- Mantle Zone (Middle): Formed by migrating neuroblasts; becomes Gray Matter.
- Marginal Zone (Outer): Formed by axons of neurons in the mantle zone; becomes White Matter.
B. Dorsoventral Patterning (The Plates)
A groove called the Sulcus Limitans appears on the inner wall, dividing the tube into:
- Alar Plate (Dorsal): Sensory component. Regulated by TGF-beta and BMPs from the roof plate.
- Basal Plate (Ventral): Motor component. Regulated by SHH (Sonic Hedgehog) from the notochord/floor plate.
- Roof and Floor Plates: Thin bridges connecting the two sides; do not contain neuroblasts.
C. Positional Changes (Ascent of the Cord)
- 3rd Month: Spinal cord extends the entire length of the embryo (ends at coccyx).
- Birth: Cord ends at L3.
- Adult: Cord ends at L1-L2.
- Clinical Significance: Lumbar puncture is safe at L4-L5 in infants to avoid cord injury.
5. DEVELOPMENT OF THE BRAIN
The cranial part of the neural tube expands to form three primary vesicles, which further divide into five secondary vesicles.
A. The Vesicles (4th - 5th Week)
| Primary Vesicle | Secondary Vesicle | Adult Derivatives | Cavity (Ventricular System) |
|---|---|---|---|
| Prosencephalon (Forebrain) | Telencephalon | Cerebral hemispheres, Basal ganglia, Hippocampus | Lateral Ventricles |
| Diencephalon | Thalamus, Hypothalamus, Retina, Epithalamus | Third Ventricle | |
| Mesencephalon (Midbrain) | Mesencephalon | Midbrain (Tectum, Tegmentum) | Cerebral Aqueduct |
| Rhombencephalon (Hindbrain) | Metencephalon | Pons, Cerebellum | Upper 4th Ventricle |
| Myelencephalon | Medulla Oblongata | Lower 4th Ventricle |
B. The Flexures
Rapid growth causes the neural tube to fold.
- Cephalic Flexure: At the midbrain level (concave ventrally).
- Cervical Flexure: Junction of hindbrain and spinal cord.
- Pontine Flexure: Between metencephalon and myelencephalon (concave dorsally); causes the alar plates to splay laterally, forming the floor of the 4th ventricle.
6. CELLULAR DIFFERENTIATION
A. Lineage
Neuroepithelium gives rise to:
- Neuroblasts: Differentiate into Neurons (lose ability to divide).
- Glioblasts: Differentiate into Astrocytes and Oligodendrocytes.
- Ependymal Cells: Line the ventricles.
Note: Microglia constitute the only CNS cells of Mesodermal origin (bone marrow).
B. Myelination
- CNS: Performed by Oligodendrocytes. Starts 4th month fetal life.
- Order: Sensory tracts myelinate before Motor.
- Corticospinal Tract: Myelination begins at birth and completes by 2 years (correlates with walking).
- PNS: Performed by Schwann Cells (Neural crest). Starts 4th month.
7. CONGENITAL ANOMALIES (EMBRYOLOGICAL BASIS)
- Neural Tube Defects: Failure of neuropore closure (Anencephaly, Spina Bifida).
- Holoprosencephaly: Failure of prosencephalon cleavage (SHH signaling defect).
- Dandy-Walker Malformation: Failure of foramina of Luschka/Magendie to open; cerebellar vermis agenesis.
- Hirschsprung Disease: Failure of neural crest cell migration to the colon.