Nervous System Development

Overview – Nervous System Development

Nervous system development is a foundational process beginning at fertilisation and culminating in the formation of a structurally complex and functionally segmented central and peripheral nervous system. From the neural tube and neural crest to brain vesicle formation and somite coordination, each step in this tightly regulated embryological timeline is clinically significant—underpinning the origins of disorders like spina bifida and sensory ganglia anomalies. This page outlines the stepwise anatomical and developmental milestones from blastocyst to fully formed nervous system.

Definition

Nervous system development refers to the sequence of embryological events that give rise to the central nervous system (CNS) and peripheral nervous system (PNS), primarily from the ectodermal germ layer.

Embryological Timeframes

Trimesters (Clinical Framing)

• First Trimester: Foundations of major organs, including the nervous system.
• Second Trimester: Maturation and elaboration of organ systems.
• Third Trimester: Rapid growth; organs become functionally independent.

Anatomical Staging (Embryological Framing – Preferred)

• Pre-Embryonic Period (Weeks 0–2): Fertilisation → Blastocyst Formation → Implantation → Gastrulation.
• Embryonic Period (Weeks 3–8): Germ layer differentiation → Organ primordia (organogenesis), including neurulation.
• Fetal Period (Week 9 → Birth): Functional growth of previously formed structures.

Blastocyst Stage (Pre-Embryonic Period)

• Day 3: Fertilised zygote becomes a morula.
• Day 7: Morula differentiates into a blastocyst which implants into the endometrium.
• Blastocyst components:
  • Trophoblast: Outer layer; contributes to placenta.
  • Inner Cell Mass (ICM): Becomes the embryo.
    • Differentiates into the bilaminar disc:
      • Epiblast (columnar): Gives rise to the entire embryo.
      • Hypoblast (cuboidal): Forms yolk sac and extraembryonic structures.

Gastrulation (Week 3 Onwards)

• Gastrulation = Formation of three germ layers from the epiblast:
  • Ectoderm → skin, nervous system.
  • Mesoderm → muscle, bone, blood.
  • Endoderm → gut epithelium, respiratory tract.
• Begins with the formation of the primitive streak on the caudal midline of the bilaminar disc.
• At the cranial end lies the primitive node, which surrounds the primitive pit.
• Epiblast cells proliferate and migrate through the pit (invagination) to form:
  • Mesoderm (middle layer),
  • Replace hypoblast with endoderm (bottom layer),
  • Surface epiblast becomes ectoderm (top layer).

Neurulation

• Neurulation = Process of neural tube formation from ectoderm.
• Midline ectoderm thickens → Neural plate.
• Neural plate folds → forms neural groove, flanked by neural folds.
• Neural folds fuse → neural tube with central cavity (neurocoele).
• Fusion starts centrally and proceeds cranially and caudally.
  • Unfused ends = neuropores, which close by week 6.
  • Failure to close leads to neural tube defects (e.g. spina bifida).
• Neural tube detaches from surface ectoderm and sinks toward mesoderm.
  • Adjacent mesoderm forms somites.

Somite Development

• Somites = Blocks of paraxial mesoderm flanking the neural tube.
• Play a critical role in segmental patterning of nervous system.
• Differentiate into three key regions:
  • Sclerotome → vertebrae and skull.
  • Myotome → skeletal muscles.
  • Dermatome → dermis of the skin.
• Segmental somite arrangement directs the organisation of spinal nerves (dermatomes, myotomes).

Neural Tube → Spinal Cord

• Post-closure, neuroblasts from the neural tube wall proliferate and differentiate.
• Layers of neural tube:
  • Mantle layer (inner): → grey matter (dorsal and ventral horns).
  • Marginal layer (outer): → white matter (myelinated axons).
• Within the mantle layer:
  • Alar plates (dorsal): Sensory neurons → dorsal horns.
  • Basal plates (ventral): Motor neurons → ventral horns.
  • Lateral horns (T1–L2): Autonomic motor neurons → axons exit via ventral roots.

Neural Crest Development

• Neural crest = Specialised ectodermal cells that migrate peripherally.
• Give rise to:
  • Sensory neurons of the dorsal root ganglia.
  • Autonomic ganglia.
  • Peripheral sensory receptors.
• Dorsal root ganglia neurons form pseudo-unipolar neurons:
  • One branch → into CNS (dorsal horn or marginal layer).
  • Other branch → peripheral receptors in skin/muscle/tendons.
• By Week 7, the spinal cord and PNS are largely organised into adult-like patterns.

Brain Development

Neural Tube Expansion (Cephalic End)

• By weeks 3–4, the cranial neural tube expands into primary brain vesicles:
  • Prosencephalon (forebrain),
  • Mesencephalon (midbrain),
  • Rhombencephalon (hindbrain).

Secondary Vesicle Formation (Week 5)

• Prosencephalon →
  • Telencephalon (cerebral hemispheres),
  • Diencephalon (thalamus, hypothalamus).
• Mesencephalon → remains midbrain.
• Rhombencephalon →
  • Metencephalon (pons, cerebellum),
  • Myelencephalon (medulla oblongata).
• A 90° cephalic flexure between forebrain and midbrain allows for bipedal posture.

Brain Folding

• At 11–13 weeks, neuroblast proliferation exceeds cranial cavity space → causes folding.
• Gives rise to gyri (elevations) and sulci (grooves).

Ventricular System Formation

• The neurocoele of the neural tube becomes the ventricular system:
  • Lateral ventricles (Telencephalon): Frontal horn, body, occipital horn, temporal horn.
  • Third ventricle (Diencephalon): Flanked by thalamus and hypothalamus.
  • Cerebral aqueduct: Connects third to fourth ventricle.
  • Fourth ventricle (Brainstem): Continuous with the central canal of spinal cord.

Pharyngeal Arches & Cranial Nerves

• Segmental structures in the head analogous to somites.
• Each pharyngeal arch contains:
  • Ectoderm → forms cranial nerves, skin.
  • Mesoderm (mesenchyme) → musculature of face and neck.
  • Endoderm → pharyngeal epithelium.
• Each arch is associated with a specific cranial nerve and muscular territory.

Summary – Nervous System Development

Nervous system development is a multi-stage process starting from the formation of the neural plate and tube, continuing with somite segmentation, and culminating in the development of the spinal cord, brain vesicles, and peripheral structures like ganglia. Critical events—such as neurulation, somite differentiation, and neuroblast migration—lay the groundwork for adult neuroanatomy and its segmental organisation. By week 7, the nervous system largely resembles its adult form, both structurally and functionally. For a broader context, see our Nervous System Overview page.