Cell Differentiation

Cell Differentiation

1. Intracellular proteins

   • pRb family
     • Retinoblastoma protein
     • Prevents excessive cell growth by inhibiting cell cycle
   • HLHs (transcription factors)
     • Neurogenic and gliogenic basic Helix Loop Helix
     • Id2 (inhibitory)
     • C/EBP
       • CCAAAT-enhancer-binding protein

2. Extrinsic cues regulating intracellular proteins

   • Ciliary neutrotrophic factor
     • Promottes neurotransmitter synthesis and neurite outgrowth
   • Leukemia inhibitory factor
     • Inhibits cell differentiation
   • Platelet-derived growth factor (PDGF)
     • Blood vessel formation
   • Fibroblast Growth Factor 2 (FGF2)
     • Prevents differentiation
   • Brain-derived neurotrophic factor (BDNF)
     • Encourages growth and differentiation of neurons and synapses
   • Neurotrophin 3 (NT3)
     • Signal cells to grow and differentiate
   • Glutamate activity

3. Mitogens (trigger mitosis)

   • O2A progenitor cells (from retina)
     • Oligodendrocytes
       • Differentiation occurs at a constant rate (regardless of demand)
     • Type-2 Astrocytes
       • Requires inducer
         • Exogenous, eg. Fetal calf serum
         • Endogenous, Cilliary Neurotrofic Factor (CNTF)
   • Treatment with PDGF = O2A oligodendroglial cell increase

4. 1st stage of differentiation = Neurites sprouting

   • Temporal differences
     • Axons before dendrites
     • Apical dendrites before basal ones

5. Experiments about role of aferentiation (input from other regions) in cortical area differentiation

   • Schlaggar and O'Leary
     • Primary somatosensory cortex in rats
       • Barrels, each receives input via thalamus from whisker
     • Section of embryonal visual cortex grafted into neonatal somatosensory cortex
       • Visual cortex develops barrel pattern
   • Mike Crair
     • If thalamocortical transmission disrupted during early development
       • Leads to abnormalities
         • Formation of superficial cortex layers
         • Differentiation of superficial cortical neurones
         • No barrels
   • Reha Erzurumlu
     • Thalamic NMDA receptors knocked out
       • Distortion of barrel pattern
     • Cortical NMDA receptors knocked out
       • Barrel pattern does not develop
   • Mriganka Sur
     • Brain "rewired" so that cells from retina projected to MGN (auditory)
       • Visual input modified development of auditory context
         • Animals were able to use their hearing cortex to "see"

6. Experiments about role of intracortical cues: WNT (wingless), BMP (bone morphogenetic protein) & FGF8

   • Fukuchi-Shimigori and Grove experiment
     • FGF8 & Emx2 = positional cues in cortex
     • FGF8 overexpression in rostral embryonal cortex
       • Barrel cortex shifts posteriorly
       • Posterior expression induces extra barrel cortex
     • Emx2 gene removed
       • Increase in FGF8
     • WNT and BMP
       • Cortex shifts dorso-ventrally