Cl23 - MCDB 4650 DEVELOPMENTAL BIOLOGY CLASS NOTES Class 23...

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MCDB 4650 DEVELOPMENTAL BIOLOGY CLASS NOTES Class 23 1 Pattern formation in the nervous system: neuronal identity and axon guidance Reading: Chp 13: 424-440 Learning Goals Be able to: Describe the general mechanisms by which axons find their targets, and give examples of kinds of molecules involved. Explain how both inhibitory and excitatory cues can determine axonal pathfinding. Interpret and design experiments that would demonstrate the importance of certain molecules in pathfinding. Both developing neurons (neural crest, cortical neurons, etc) and their axons migrate to their final positions via some of the same mechanisms. Migration along the basal lamina involves interactions between extracellular matrix (ECM) components and surface receptors on either cells or axons. At the tip of the growing process is a growth cone, which is both the engine and the steering apparatus for outgrowth. It is a highly mobile lamellipodium, which appears to be feeling its way along as the axon grows. Some of the molecules involved in migrations along basal lamina, as for non-neuronal migrations, are fibronectin and laminins in the ECM and integrins on cell surfaces. These molecules are believed to often offer relatively non-specific or short-range guidance since they are widely expressed in the developing nervous system, though there may well be exceptions. Most growth cones follow paths pioneered by other neurons, so that bundles of axons called fascicles are formed as additional axons grow out toward a particular target. Thus, pathfinding by later axons can be mediated by homotypic interactions between the cells, involving N-CAM, specific cadherins, and fasciclins. However, the axon of the first neuron to follow a new pathway, called a pioneer neuron, cannot use this mechanism. Note that the problem faced by a pioneer axon, sometimes involving traversing a large distance and multiple different cellular environments is significant. Many of the above molecules are widely expressed in the developing nervous system and are probably generic axon growth promoters, with little instructive information about pathfinding (but create a permissive region for axons to grow in). However, specific members of these gene families, or alternate splice forms, modifications, etc. may be important in guidance. What
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Cl23 - MCDB 4650 DEVELOPMENTAL BIOLOGY CLASS NOTES Class 23...

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