Cell Proliferation

Cell Proliferation

1. Inter-cellular signalling

   • Direct cell-cell contact
     • Electric fields
     • Adhesion molecules
       • Cadherins
         • Calcium-dependent
         • Class I transmembrane proteins
       • Integrins
         • Transmembrane heterodimers
         • Attach cytoskeleton to extracellular matrix
   • Via secreted ligands
     • Volume transmission
       • = diffusion of neurotransmitters through brain extra-cellular fluid
         • Released at points remote from target cells
         • Activates extrasynaptic receptors
         • Longer time course than single synapse
       • Types
         • Netrins
           • Proteins for axon guidance
         • Ephrins
           • Cell-surface molecules
         • Non-synaptic hormones
         • Neurotransmitters
         • Trophic factors
           • Allow neurons to develop and maintain connections
     • Synaptic transmission

2. Signalling molecules in developing CNS

   • Retinoid acid
     • Mediates function of vit. A for growth
   • Fibroblast growth factor
     • Activate pathways through tyrosine kinase receptors
   • Transforming growth factor
     • Protein of cytokine family
   • Sonic Hedgehog
     • Diffuses to form a concentration gradient
       • Has different effect on developing cells depending on concentration
   • Wnt
     • Increases Beta-catenin
       • Initiates transcriptional activity of proteins

3. Methods of studying neurogenesis (Cell fate mapping/cell lineage analysis)

   • Cell labelling
     • HRP
       • Labelling using Horseradish Peroxidase, which allows for electron microscope observation
     • Rhodamine & fluorescein
       • Offer longer wavelength, allowing for multicolour staining
     • BrdU (Bromodeoxyuridine)
     • 3H-TdR (Tritiated Thymidine)
     • Cre-Lox
       • Allows DNA modifications at specific sites
     • "Caged" fluorescent peptides
     • Fluorescent protein mRNA
   • Cell abrogation/impairement
     • Pronase
     • DNAase
     • Ricin A chain
     • Cre-Lox (Tamoxifen & RER)
     • siRNA

4. Neural tube differentiation

   • Germinal Neuroepithelium
     • One cell thick (gets thicker)
     • Progenitor cells divide from luminal (ventricular surface) to marginal zone
   • Ventricular zone
   • Subventricular zone
     • Ganglionic eminences of ventral telencephalon (lateral, medial and caudal)
       • Primordia of Basal Ganglia

5. Cell proliferation

   • 1. Radial Glia in VZ extend process up to pia
   • 2. Nucleus of glia migrates up to pia
     • Cell's DNA copied
   • 3. Nucleus with 2 copies of DNA migrates back to VZ
   • 4. Glia retracts process
   • 5. Cell divides in 2
     • Horizontally
       • Notch-1 migrates up
       • Numb stays at bottom
     • Vertically
       • Cells with both Notch-1 and Numb keep dividing