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BIOLOGY 2C03 (138)
Kim Dej (45)

Development III

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Kim Dej

Outline of Lecture 12 (02-20 E; Kolodkin) Development III (Axon Guidance) I. Principles of axon guidance A) Historical perspective: early evidence of axonal guidance cues - Cajal and Harrison observe dynamic nature of axonal growth cone - Sperry demonstrates topographic mapping in retina-to-tectum - Spinal cord inversion does not affect how motor axons select peripheral pathways B) Sequence of events: pathfinding, target selection, synapse formation and refinement II. Neuronal growth cone organization - Growth cone has filopodia and lamellipodia - Actin: found in growth cone, undergoes treadmilling via myosin and actin polymerization; adhesive molecules and myosin mediate membrane protrusion - Microtubules: found polymerized in axon shaft, fills in voids in growth cone when actin is attached to membrane complexes in response to extracellular cues (this is the method of growth cone advance) - Individual filopodia can steer entire growth cone via mechanism above III. Molecular regulation of axonal guidance (see also Lec 18 for list of sources of guidance cues) A) RHO GTPases and cytoskeleton - RHO family members (Cdc42, Rac, Rho) are GTPases that modulate actin cytoskeleton and are regulated by GEFs and GAPs - Cdc42 (filopodia)  Rac (lamellipodia)  Rho (stress fibers, focal adhesions) - Cdc42 and Rac promote axon and dendrite growth, whereas Rho limits it B) ECM cues (a form of short range guidance) - Laminin in ECM are permissive to pathfinding (binds integrin receptors) C) Guidepost neurons (a form of short range guidance) - Guideposts he
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