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Neuronal Development

Overview of Lecture Content

• Focus on connections between neurons and development of the cortex.
• Learning outcomes include:
    - Migration of neuroblasts to final positions in the cortex.
    - Development of neurons from neuroblasts through axon guidance.
    - Formation of synapses with target cells (other neurons or muscle cells).
    - Consequence of failed synapse formation leading to apoptosis.
    - Formation and role of glial cells in the CNS (central nervous system).
    - Discussion of white matter and gray matter in histology.

Neuronal Migration and Development of the Cortex

Embryonic Development in Chickens

• Chick embryos serve as a model due to their flat development, unlike folded mouse embryos.
• Series of images depict the developmental stages from young to old embryos, arranged anterior to posterior.
    - Primitive Streak: Present in all images; longest in the youngest embryo, indicating progression from cranial to caudal as gastrulation occurs.
• Neural Induction: Concurrent with gastrulation, leads to regions of ectoderm becoming neural tissue.
    - Formation of neural folds, which begin to lift and undergo neurulation simultaneously with gastrulation.
• Somite Development: Observed formation of somites from mesoderm, which increase in number as embryos mature.

Formation of the Cerebral Cortex

• The cortex, the largest part of the brain, requires precise neuron migration to develop layered structures.
• Radial Migration: Neurons generated from progenitor cells migrate along glial cell processes to form cortex layers.
    - Progenitor Cells & Radial Glial Cells: Cells divide at the ventricles and extend processes toward the basal surface of the brain.
    - Layer Formation: Begins with three zones - preplate, intermediate zone, and ventricular zone.
      - Preplate: Contains initial neurons (Cajal-Retzius and subplate cells).
        - Splits into distinct zones with Cajal-Retzius cells in the marginal zone and subplate cells in the subplate.
• Cortical Plate Development: New neurons migrate through the subventricular zone and utilize glial processes to climb towards cortical plate.
    - The order of migration: Older neurons occupy deeper layers, while younger neurons migrate to outer cortical layers.

Tangential Migration

• An additional pathway for neuron migration, especially for interneurons.
• Neurons born in the ganglionic eminence migrate toward the cortex, contributing to specific layers.

Control of Radial Migration

• Rheelan: Secreted by Cajal-Retzius cells, regulates migration by signaling neuroblasts to stop once they reach it.
    - Mutations in the rheelan gene: Cause abnormal cortical layering and balance issues, exemplified by rheelan mouse studies.
    - Rheelan is crucial for the inside-out layering of cortical neurons.

Schematic Illustrations of Cortical Layering Process

• Describes radial glial and progenitor cells within the developing brain:
    1. Neural Stem Cells: Undergo symmetrical proliferation.
    2. Asymmetrical Proliferation: Generates neuroblasts and additional progenitor cells.
    3. How neuroblasts climb glial processes to populate cortex layers, with Cajal-Retzius cells forming the marginal zone and subplate continuing to develop layers as neuroblasts migrate in.
    4. Inside-Out Lamination: Older neurons establish deeper layers while younger ones position themselves closer to the surface.
    5. Mention of outer radial glial cells that do not extend entirely to the apical surface, relevant later in neurogenesis.

Conclusion

• The lecture emphasizes the complexity of neuronal migration and the processes leading to the layered structure of the cortex, including the roles of various cells and molecules. Understanding these fundamental concepts is crucial for grasping neuronal development and the functioning of the CNS.