Neural Development 2: Neuronal Connections

Formation of the Cortex of the Brain

  • Neuroblasts migrate along radial glia to the outer cortex (radial migration).
  • Preplate separates into marginal zone and subplate; cortical plate forms in-between.
  • Neuroblasts move into the subventricular zone, then use radial glia to migrate radially.
  • Cortical plate forms between marginal zone (Cajal-Retzius cells) and subplate neurons.
  • Neurons migrate to form the cortex in an inside-out manner (newer cells further out).
  • Tangential migration from ganglionic eminence contributes interneurons to specific layers.
  • Cajal-Retzius cells secrete reelin, signaling neuroblasts to stop migration; mutations cause abnormal layering.

Axon Guidance

  • Neurons connect by extending neurites with growth cones.
  • Growth cones are guided to targets, similar to cell migration.
  • Environmental cues can be attractive or repulsive, acting at long or short ranges.
  • Intracellular responses affect microfilaments, causing polymerization/depolymerization of actin.
  • Growth cones use cell adhesion; pioneer axons guide others.
  • Retinal ganglion neurons use Eph receptors and Ephrin ligands for retinotopic mapping.
  • Some axons cross the midline and avoid re-crossing, involving Slit and Robo.
  • Comm prevents Robo expression until midline crossing, where netrin-frazzled signaling downregulates Comm, allowing Robo expression and Slit repulsion.

Synaptogenesis and Neuromuscular Junctions

  • Synaptogenesis involves contact, stabilization, adhesion, signaling, and maturation.
  • Forming a neuromuscular junction requires signaling between cells to develop specializations.
  • At neuromuscular junctions, multiple axons converge, but many are eliminated; the surviving axon branches and is sheathed by Schwann cells.

Regulation of Cell Numbers and Apoptosis

  • More than half of neurons die during normal development, regulated by target tissue innervation.
  • Motor neurons that fail to make synapses undergo apoptosis; mutations in Fz3 can cause stalled migration and apoptosis.
  • Target tissue produces survival factors (neurotrophins) like NGF, which are endocytosed and retrogradely transported to the cell body.
  • Neurotrophins also play a role in axon guidance and synapse formation.
  • Different neuronal populations respond to different neurotrophins (e.g., NGF, BDNF).

Gliogenesis and Histology

  • Neurogenesis is followed by gliogenesis, with changing expression patterns.
  • The central nervous system consists of grey matter (neuronal cell bodies) and white matter (axon tracts).
  • Peripheral nervous system includes sensory, motor, and interneurons.
  • Ganglia are aggregations of neuronal cell bodies with satellite cells.
  • Peripheral nerves consist of axons (sensory and motor) with myelinating Schwann cells.