Basic knowledge of how nerve connections are established during development is essential for the development of clinical therapies in nerve repair. The correct wiring of the nervous system relies on the ability of axons and dendrites to locate and recognize their appropriate synaptic targets during development.
Pathfinding by growing axons is guided by extracelluar guidance factors. Recently, it has become clear that guidance cues can trigger rapid and local synthesis, degradation and endocytosis of protein s, providing a fast and flexible way for growth cones to respond to cues in their microenvironment and adapt their responses to changing conditions.
Key questions raised by these data are
- what particular proteins are translated in response to axon guidance cues
- do different guidance cues elicit dynamic changes in different sets of proteins
- how do these proteins control the chemotactic turning behaviour of a growth cone
The present proposal addresses these questions using a comparative proteomic app roach involving C-terminal puromycyl-tagging of newly synthesized proteins in developing chick retinal growth cones. Once identified, the function of the cue-induced nascent protein(s), will be approached using gene manipulations and protein knock-down experiments in vitro and in vivo in the Xenopus retinotectal system.
Prof. Holts laboratory provides an excellent environment to study all of these aspects of axon guidance both in vitro and in vivo. Moreover, moving to the host institute will complement my scientific training and is essential to achieve my goal of becoming an independent researcher in neurobiology.
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