Neural Development 2: Neuronal Connections
- 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.