Architecture of the CNS

• Dorsal-ventral specification


  Specification of the neural tube along the dorsal-ventral axis

  
• Sonic hedgehog


  • Involved in dorsal-ventral specification of the neural tube
• Dorsalin


  • Involved in dorsal-ventral specification of the neural tube

  
• Pax 7


  • Involved in dorsal-ventral specification of the neural tube

  
• Pax 6


  • Involved in dorsal-ventral specification of the neural tube

  
• Nkx6.1


  • Involved in dorsal-ventral specification of the neural tube

  
• Motor neurons


  • Develop from the neural tube
• Germinal neuroepithelium


  A layer of rapidly dividing neural stem cells that is one cell layer thick

  
• The nuclei of cells in the germinal neuroepithelium move with the cells as they move through the cell cycle
• If mammalian neural tube cells are labelled with radioactive thymidine during early development, 100% of them incorporate this base into their DNA

  
• Certain cells stop incorporating DNA precursors, indicating they are no longer participating in the cell cycle
• These cells migrate and differentiate into neuronal and glial cells outside the neural tube

  
• If dividing cells in the germinal neuroepithelium are labelled with radioactive thymidine, their progeny can be found in the outer cortex in the adult brain, indicating they migrated from the germinal neuroepithelium

  
• Neuron's birthday


  1. Neuroepithelial stem cell divides vertically

  2. Daughter cell connected to lumen remains a stem cell

  3. Other daughter cell migrates and differentiates

  4. Time of vertical division is the neuron's birthday
• Different types of neurons and glial cells have birthdays at different times
• Cells with earlier birthdays migrate shorter distances, cells with later birthdays migrate through these layers to form more superficial regions of the cortex
• Ventricular zone


  The original germinal neuroepithelium
• Mantle zone


  The layer that forms around the original neural tube as migrating cells are added

  
• Marginal zone


  The cell-poor layer where neurons make connections and send axons away from the lumen
• Grey matter


  The mantle zone containing the cell bodies
• White matter


  The axonal marginal layer
• Nuclei


  • Clusters of neurons that serve as relay stations between the outer layers of the cerebellum and other parts of the brain

  
• External granular layer


  • A new germinal zone where neuronal precursors migrate to form

  
• Purkinje neurons


  • Distinctive and large neurons, the major cell type of the cerebellum
  • Secrete sonic hedgehog to sustain division of granule neuron precursors
  • Have an enormous dendritic arbor and form up to 100,000 synapses
  • Emit a slender axon that connects to neurons in the deep cerebellar nuclei

  
• Glial guidance


  Important for positioning young neurons, neurons ride a "glial monorail" to their destinations
• Astrotactin


  • A protein that neurons adhere to on glial cells, important for neuronal migration

  
• Mice deficient in astrotactin have slow neuronal migration rates, abnormal Purkinje cell development, and problems coordinating their balance
• Over 30 mutations affecting the arrangement of cerebellar neurons in mice have been identified, many causing balance issues
• Neocortex


  The second zone of neurons that forms at the outer surface of the brain
• The neocortex eventually stratifies into six layers of neuronal cell bodies, not completed until middle childhood
• The cerebral cortex is organised horizontally into over 40 regions that regulate anatomically and functionally distinct processes
• Cerebral cortex formation


  1. Stem cells in the ventricular layer give rise to neurons and glial cells in any of the cortical layers

  2. Early neuronal precursors migrate to layer 6, late precursors migrate farther to layers 2/3

  
• Cerebral cortex


  • The outer layered structure of neural tissue
  • Massive expansion of the surface and elaboration of connections in humans originates from developmental events
  • Understanding genetic regulation of cell number, migration, and differentiation is critical

  
• The cerebral cortex has expanded significantly in humans relative to other hominids, including the introduction of new regions like the frontal and temporal lobes
• Basic principles of brain development are conserved across mammals, but modifications of developmental events during evolution produce quantitative and qualitative changes
• Cortical expansion


  Occurs primarily in surface area rather than thickness, neocortex can comprise up to 80% of brain mass
• The neocortex is subdivided into distinct cytoarchitectonic areas with neurons organized in horizontal layers and vertical columns, which have increased in number, size, and complexity during cortical evolution

  
• Diminishing programmed cell death or increasing neural stem cell proliferation in the ventricular zone can result in a larger cortical surface that forms incipient convolutions
• Injecting humans with BrdU to detect adult neurogenesis is generally unethical, but in some cancer patients it has been used to show new neurons are generated in the hippocampal dentate gyrus