Prosencephalic Development

Introduction

• Prosencephalon (forebrain) development occurs 3–5 weeks post-conception (p/c).
• Neural tube at rostral end forms three primary vesicles:
  1. Prosencephalon (forebrain): Telencephalon + Diencephalon
  2. Mesencephalon (midbrain)
  3. Rhombencephalon (hindbrain): Metencephalon + Myelencephalon
• Formation of three flexures:
  • Mesencephalic (midbrain)
  • Pontine (hindbrain)
  • Cervical (junction hindbrain/spinal cord)
• Ventral induction involves three sequential steps:
  1. Formation
  2. Cleavage
  3. Midline development

1. Prosencephalic Formation

• Occurs around 5 weeks gestation.
• Divides into two secondary vesicles:
  • Telencephalon:
    • Gives rise to cerebral hemispheres, putamen, caudate nucleus.
  • Diencephalon:
    • Gives rise to thalamus, hypothalamus, globus pallidus, optic vesicles.

2. Prosencephalic Cleavage

• Occurs around 35 days p/c.
• Prosencephalon initially surrounded by solid meninx primitiva, essential for proper development.
• Cleavage into left and right telencephalic vesicles:
  • Driven by increased apoptosis + decreased proliferation.
• Controlled by complex signaling pathways along midline:
  • Dorsal midline: BMP and WNT signals
  • Rostral midline: Fibroblast Growth Factor (FGF)
  • Ventral midline: Sonic Hedgehog (SHH)
• BMP and SHH signaling:
  • Antagonistic roles in dorsoventral patterning.
  • Disruptions cause holoprosencephaly spectrum disorders.

3. Midline Prosencephalic Development

• Lamina terminalis: anterior tip of neural tube.
• Commissural plate (dorsal lamina terminalis):
  • Origin of major forebrain commissures (fiber connections between hemispheres).
• Formation of commissures:
  • Anterior commissure: Week 10
  • Hippocampal commissure: Week 11
  • Corpus callosum: starts Week 12–13
• Corpus callosum growth details:
  • Glial "sling" guides callosal fiber crossing at midline.
  • Callosum expands rapidly by Weeks 14–15, all five segments present:
    • Rostrum, genu, body, isthmus, splenium
  • Initially short (rostral-caudal); reaches full length by Weeks 19–20, then thickens.
  • Splenium growth guided by hippocampal commissure.
  • Posterior growth driven by rapid frontal cortex expansion, pushing splenium posteriorly.
  • Failure in any of these steps may cause corpus callosum agenesis/hypogenesis.
• Fornix and septum pellucidum stretch as anterior/hippocampal commissures separate.

Cavum Septi Pellucidi & Cavum Vergae

• Derived from septal leaflets of the commissural plate.
• Initially form one cavity; divides into:
  • Cavum septi pellucidi (anterior): anterior to foramen of Monro
  • Cavum vergae (posterior): behind plane of foramen of Monro
• Closure timing:
  • Walls appose back-to-front starting around 6 months gestation.
  • Completely closes in 85% of infants by 3–6 months postnatally.
• Imaging significance:
  • Presence of cavum septi pellucidi confirms at least partial corpus callosum development.
  • Absence does not necessarily indicate corpus callosum agenesis.

Cavum Velum Interpositum

• Potential space within tela choroidea of third ventricle:
  • Superior boundary: fornices, hippocampal commissure.
  • Inferior boundary: tela choroidea (roof of third ventricle).
• Anterior extension: up to foramen of Monro.
• Contains internal cerebral veins, draining into vein of Galen under splenium.
• Posterior extension: into pineal region beneath splenium.
• Enlargement can:
  • Displace internal cerebral veins inferiorly.
  • Result in concave upper boundary due to downward displacement of fornix columns.
  • Create diagnostic challenges, mimicking cystic malformations.

Clinical Implications

• Proper formation, cleavage, midline development essential for normal cerebral architecture.
• Signaling disruptions (BMP, SHH, WNT, FGF) cause midline disorders, most notably holoprosencephaly.
• Corpus callosum agenesis/hypoplasia common consequence of midline development disruptions.