1. Key
    1. intracellular
    2. secreted proteins
    3. membrane-bound
    4. parts
    5. protein receptors
    6. Relationships
      1. Blocks, repels
      2. Activates, attracts
      3. Reciprocal Gradient
  2. Floor Plate
  3. Notochord
  4. Ectoderm
  5. Roof Plate
  6. Sensory Neurons
  7. Motor Neurons
  8. Commisural Neurons (Pre-Commisural)
  9. Commisural Neurons (Post-Commisural)
  10. To Brain
  11. Cadherins
    1. Ca2+ based cell-adhesion proteins
    2. Many types
      1. Cells connect homophillically -> attach to others with the same type Cadherin expression
      2. Different types for regional separation
    3. Beta-Catenin
      1. when overexpressed, forms a much larger brain
      2. unknown details, suggested that it elongates proliferative period
  12. Early Polarity
    1. SHH
      1. Sonic Hedgehog
      2. Secreted by Notochord
        1. induces formation of Floor Plate
      3. Secreted by Floor Plate
        1. induces formation of Motor Neurons
    2. BMP
      1. During Gastrulation
        1. Bone Morphogenic Protein 4
        2. Secreted by most cells
        3. Receptors activated by BMP-4 fate cells to become epidermal
      2. Post Gastrulation
        1. Released from Neural Crest
          1. Induces formation of Roof Plate
        2. Released from Roof Plate
          1. Induces formation of Sensory Neurons
    3. Noggin
      1. Expressed at gastrulation
      2. Expressed by mesodermic cells
      3. Prevents binding of BMP-4
      4. Allows cells to follow natural fate -> to become neurons
  13. Proliferation
    1. Notch1
      1. At alar pole of cell
        1. allows cell to travel away from mitotic phase
    2. Numb
      1. At basal pole of cell
        1. keeps cell bound to ventricular floor
        2. keeps cell in mitotic phase
    3. Horizontal vs. Vertical Cleavage determines which is active
  14. Migration
    1. Reelin
      1. Secreted by Cajal-Retzius cells
        1. first cells present, before neurogenesis
      2. Causes migrating neuroblasts to migrate past
      3. allows for inside-out neurogenesis
    2. Prokineticin
      1. Attractant
      2. Released by Olfactory Bulb
    3. Slit-Netrin
      1. Slit
        1. Repellant
        2. Secreted by Septum
          1. repels Olfactory cells migrating towards Bulb
          2. repels Mitral cell growth cones from Bulb
        3. Floor Plate
          1. Released locally
          2. Induces movement of Commisural growth cones out of Floor Plate
      2. Robo
        1. Receptor for Slit
        2. Induces growth or movement down Slit gradient
        3. Olfactory Bulb
          1. Expressed in Granule Cells migrating to Olfactory Bulb
          2. Expressed in Mitral cell Growth Cones coming from Olfactory Bulb
        4. Floor Plate
          1. Activated in Commisural Growth Cones
          2. dimerizes with DCC until DCC is saturated
      3. DCC
        1. Dimerizing receptor for Netrin
        2. Induces growth cone to grow up Netrin gradient
        3. deactivated by dimerization with Robo
      4. Netrin
        1. Attractant
          1. under normal situations
        2. At Floor Plate
          1. Attracts Commisural Neurons
        3. Repellant
          1. under altered cAMP levels
    4. wnt4
      1. Gradient Increasing up brainstem to brain
      2. attractant
        1. post-commisural neurons follow this
        2. pre-commisural are immune
    5. fz3
      1. Disorients neurons
    6. Semaphorins
      1. Chemorepellant
      2. Causes collapse of Philapodia & Lamellopodia
    7. Oligodendrocytes & Myelin
      1. Repellant
      2. On contact, growth cones collapse & retreat
    8. Astrotactin
      1. Created by neuroblasts
      2. induces adhesion to Radial Glial Processes
    9. Extra Cellular Matrix
      1. Laminin & Fibronectin
        1. In Cerebellum
          1. Released to help migration of Granule cells from IVth ventrical to Pial surface
        2. Only found in E.C.M.
        3. Neural Crest
          1. Neural crest follows gradient to form Spinal Ganglia
      2. Integrin
        1. Expressed in Granule cells at Cerebellum
          1. Migration from IVth Ventrical @ Subventricular Layer to Pial Surface
      3. CSPG's
        1. Chondroitin Sulfate Proteoglycans
        2. repellant
        3. Optic Development
          1. Initially fills whole Optic Cup except nerve head
          2. Induces movement of axons towards nerve head
          3. Also at more dorsal regions of optic tract
          4. creates chronotopic organization b/c new growth cones are repelled towards ventral end
    10. Ephrins
      1. EphA
        1. Receptor for EphrinA
        2. Repelled
        3. Temporal (+) - Nasal (-) gradient in Retina
        4. Rostral (+) - Caudal (-) gradient in Thalamus
      2. EphrinA
        1. Secreted in Tectum
        2. Repellant
        3. Caudal (+) - Rostral (-) gradient in Tectum
        4. Caudal (+) - Rostral (-) gradient in Striatum
      3. Partial Decussation @ Optic Chiasm
        1. Ephrin B2
          1. High levels in chiasm
          2. Repellant
        2. EphB1
          1. Receptor for Ephrin B
          2. Induces repulsion -> sends axons ipsilateral
        3. Zic2
          1. Activates EphB1
        4. Islet2
          1. Deactivates Zic2 and EphB1
          2. Induces contralateral growth