1. Development of Neural Circuits Lesson 5

2. Stages of Cellular Activity n 6 distinct stages 1. Neurogenesis 2. Cell migration 3. Differentiation 4. Synaptogenesis 5. Neuronal cell death 6. Synaptic rearrangement ~

3. Neurogenesis n Precursors (stem) cells l Neural plate & tube stages l Neural tube’s ventricular zone l Induction signals ~

4. Symmetrical Mitosis n Results in 2 stem cells l Slow & unlimited division n Mediated by notch protein l Required for self-renewal l Stem & progenitor cells ~

5. Asymmetrical Mitosis n Results in neuroblast + progenitor n Neuroblasts l Differentiate into neurons & glia n Progenitors: l rapid, but limited division n Mediated by numb protein l Asymmetrically distributed in mitosis l Inhibits notch protein ~

6. Neuronal Migration: PNS n Neural crest  PNS l Initial position anterior-posterior factor n Epithelial  mesenchymal transition l Snail1 & 2   adhesion molecules n Guided by l cell adhesion molecules (CAMs) l Secreted peptide hormones l Along musculoskeletal tissues ~

7. Neuronal Migration: CNS n Neural tube  CNS l Primarily along radial glia l Some along axons l CAMs ~

8. Cell Migration n Long-distance migration l Along radial glia l Tangentially to other brain areas n Cerebellar neuroblasts l Mesoencephalon  l Rhombencephalon ~

9. Cell Differentiation n Stem cells  neurons & glia l Many types of each n Cell-to-cell signaling l Particularly young precursor cells l BMPs, shh, Wnt induction signals n Cell autonomous l Transcription regulation l bHLH proneural genes  neurons l Inhibit bHLH  glia ~

10. Construction of Circuits n Linkage of neurons in different regions l Growth of axon from origin to target l Formation of appropriate synapses n Cell-to-cell signaling l Tropic factors l Trophic factors ~

11. Axon Guidance n Axonal growth cone l Filopodia n Decision points l Decussate or not n Chemical cues l Ligands/receptors ~ n Non-diffusable cues l CAMs l Tropic & trophic n Diffusable chemical signals l Attraction netrins l Repulsion Semaphorins ~

12. Synaptogenesis n Superior cervical ganglion (PNS) l  eyes l  ear blood vessels n After axons reach target l Establish synapse l Retract & regrow l Do not form synapse ~

13. Synaptogenesis n Neurotropic factors l Ephrins & cadherins l Specificity  ligand/receptor types n Neurotrophic factors (neurotrophins) l After synapse formation l Cell-to-cell signals l Nerve growth factor (NGF) l  neurite growth ~

14. Apoptosis n Neuronal cell death l programmed cell death l 20-80% of neurons in a region l lack of neurotrophic factors n Wrong or no connection l neurons wither & die ~

15. Synaptic Rearrangement n Competition l elimination of synapses l formation of new synapses n Activity-dependent l Neurotransmitter release n Losing axon retracts l May strengthen synapse at other targets l Winner  synapses at target ~