To generate a neural circuit, neurons send out a specific number of axons and dendrites along stereotyped paths towards their final targets. Once their targets are reached, these mature neurons cease growing, stabilize their morphology, and switch to a state of maintenance. Great strides have been made in understanding the molecular mechanisms underlying axon outgrowth and guidance. However, few molecules have been found that stabilize neuron morphology once initial outgrowth and guidance are complete. Molecules acting in such a process may be regulated in interesting ways during axon regeneration.The majority of research in this area has been done in vitro. This proposal aims to complement these approaches with the power of genetics and the simplicity of the nematode, Caenorhabditis elegans. In particular, two genes characterized by the Bargmann lab, sax-1 and sax-2, have been implicated in the inhibition of neurite (axon/dendrite) outgrowth in mature neurons. Specific cellular, molecular and genetic experiments are proposed that will further investigate the role of sax-1 and sax-2 in the inhibition of neurite outgrowth and identify additional genes functioning along side or in parallel to sax-i and sax-2 in mature neurons.
