week 6

• Neuronal cells migrate to their final position in the cortex
• Neuronal migration


  1. Neuroblasts generated from progenitor cells migrate along the process of the apical progenitor cell (radial glia) to the outer part of the cortex

  2. Radial migration
• Radial glia (progenitor cells)


  • Extend glia from the ventricular/apical surface to the basal/outer surface of the brain
• Layers of the cortex


  • Preplate (Cajal-Retzius and subplate cells)
  • Intermediate zone
  • Ventricular zone
• Formation of the cortical plate


  1. Preplate separates into marginal zone and subplate

  2. Cortical plate forms in-between
• Cortical lamination


  1. Neuroblasts migrate radially for cortical lamination

  2. Neurons migrate to form the cortex (cortical plate) in an inside-out manner
• Tangential migration


  • Important source of neurons to the cortex
  • Neurons develop into interneurons, in specific layers of the cortex
• Reelin


  Molecule secreted by Cajal-Retzius cells that signals neuroblasts to stop migration
• Mutations in the reelin gene cause defects in radial neuronal migration
• Growth cone


  Structure at the end of a developing axon
• Axon guidance


  • Similarities between axon guidance and cell migration
  • Growth cone expresses many receptors
  • Signalling molecules (ligands) are expressed by environment
  • Intracellular response to these ligands can affect behaviour of growth cone
• Changes in the growth cone


  1. Disassembly of actin filaments

  2. Polymerisation of actin filaments

  3. Actomyosin contraction
• Growth cones and axons use cell adhesion to help guide them
• Pioneer axons


  First axons to grow, used as a guide by other axons
• Repulsive adhesive cue in retinal ganglion neurons


  • Different level of expression of Eph receptor across retina, and gradient of Ephrin ligand in target site creates retinotopic map
• Axons crossing the midline


  1. Slit and robo are two guidance molecules involved

  2. Comm prevents Robo from being expressed at the cell membrane

  3. When axons reach the midline, increased netrin-frazzled signalling triggers down-regulation of Comm

  4. Then Robo is no longer degraded, but expressed on growth cone membrane

  5. Growth cone responds to slit repulsion, and the axon stays away from the midline
• Synaptogenesis


  1. Contact between the cells

  2. Stabilise the contact

  3. Cell adhesion

  4. Signalling

  5. Maturation
• Neuro-muscular junction


  • Importance of signalling between the cell types in developing a neuro-muscular junction
  • Both cells need to develop specialisations at this synaptic site
• Neuromuscular junctions


  1. Other axons converge on same synaptic site

  2. Not all survive - many axons are eliminated

  3. Surviving axon can branch to form a complex neuromuscular junction

  4. Surviving axon is sheathed by Schwann cells (myelinated)
• Apoptosis


  Process that triggers neuronal cell death
• Axons of motor neurons don't make synapses on muscle


  Fewer motor neurons survive, as they have not made connections with muscle
• Removing a limb bud


  Fewer motor neurons survive
• Adding a limb bud (increasing target size)

  More motor neurons survive
• Neurotrophins


  Survival factors produced by the target tissue
• Transport of neurotrophic signals to cell body


  Endocytosis from the axon growth cone and transported to the cell body of the neuron
• Retrograde transport


  Transport back up the axon, opposite to anterograde
• Roles of neurotrophins


  • Neuronal survival
  • Axon guidance
  • Establishing and maturing synapses
• Different neuronal populations respond to different neurotrophins
• Development of glial cells


  1. Neurogenesis is followed by gliogenesis

  2. Changing expression patterns over time signal change from neural production to glial generation
• Regions of the central nervous system


  • Regions with neuronal cell bodies - grey matter
  • Regions with axon tracts (and oligodendrocytes) - white matter
• Cell types in the peripheral nervous system


  • Sensory neurons
  • Motor (autonomic) neurons
  • Interneurons
• Ganglia


  Aggregation of neuronal cell bodies, and satellite cells
• Peripheral nerve


  Axons of sensory and motor neurons, with myelinating Schwann cells
• Neural crest are only found in vertebrates, and form a variety of cell types
• Neural crest development


  1. Develop from the neural plate border

  2. Undergo an epithelial-mesenchymal transition

  3. Delaminate to leave the neural plate/tube
• Neural crest migration pathways


  • Cranial
  • Vagal
  • Trunk
  • Sacral
• Cranial neural crest


  • Can give rise to connective tissues (incl bone), and neural tissues
• Vagal neural crest


  • Form most of the enteric nervous system, and parts of the heart
• Trunk neural crest


  • Form neural tissues, adrenal medulla and melanocytes
• Sacral neural crest


  • Form parasympathetic ganglia, and some enteric neurons