Principles of Neuronal Migration 6

Principles of Neuronal Migration

  • Neuronal Migration Overview

    • Neurons are typically born far from their final resting place; migration is crucial for proper brain development.
    • Key types of migration: gliophilic, neurophilic, and biphilic.
    • Example: Migration of granule cells in the cerebellum.

  • Basic Migration Mechanisms

    • Cerebral Cortex as a Model
    • Neurons may need to migrate distances of 5-6 mm, which is significant relative to their size (15 microns).
    • Diagram shows brain development over time, indicating…
      • Earliest born neurons occupy deeper layers.
      • Later born neurons end up in more superficial layers.

  • Cellular Migration Types

    • Gliophilic Migration
    • Neurons migrate along radial glial cells.
    • Radial glial cells span from the ventricular zone to the cortical surface.
    • Neurons use glial tracks like railroad tracks for migration, preserving neighbor relationships.
    • Neurophilic Migration
    • Neurons bypass glial cells to follow existing neuron tracks.
    • Tangential migration occurs, especially for interneurons originating from the medial ganglionic eminence.
    • Biphilic Migration
    • Combines both gliophilic and neurophilic migration.
    • Example shown with the anatomy and functions of granule cells in the cerebellum.

  • Detailed Process of Migration

    • Granule Cells in the Cerebellum
    • Born in the rhombic lip, migrate to the ventricular zone; they undergo cell division here.
    • Initially bipolar during this process; postnatally switch to gliophilic migration along Bergmann glial fibers.
    • Unique movement of the nucleus allows successful migration to final location.
    • Important Facts:
      • Granule cells specialize in targeting Purkinje cells for motor control.
      • They undergo a highly coordinated migration process that influences brain anatomy.

  • Cell Adhesion Molecules

    • Important for the migration process and neuronal-glial interactions.
    • Example molecules:
    • N-CAM (Neuronal Cell Adhesion Molecule)
      • Present but not relevant for gliophilic migration.
    • NCAM-PSA (polysialylated form)
      • Specifically relates to gliophilic migration in the cerebellum.
    • Ng-CAM (Neuron-Glia Cell Adhesion Molecule)
      • Important for early neurophilic migration.
    • Cytotactin
      • Important for later migration along glial structures.

  • Consequences of Migration Failure

    • Failure of migration due to genetic or environmental factors can lead to malformations.
    • Examples:
    • Lissencephaly: Smooth brain surface due to fewer ontogenic columns with normal thickness; results in seizures, intellectual disability.
    • Polymicrogyria: Excess convolutions but thinner cortex.
    • Radiation Effects: Observed in children exposed to radiation during gestation, leading to microcephaly and abnormal migration of neurons.

  • Summary

    • Neuronal migration is critical for developmental patterns in the brain and may occur via specific pathways supplied by glial or neuronal structures.
    • Both genetic and environmental influences can impact the successful migration of neurons, ultimately affecting brain structure and function.
    • Understanding neuronal migration has implications for addressing developmental disorders in neurology.