Only recently have molecules that guide axon migration been discovered. One of the first was the UNC-6 netrin from the nematode Caenorhabditis elegans. Other guidance molecules interact with and affect UNC-6 activity, and their discovery and the genetic dissection of their interactions are a main focus of this application. Examples include a C. elegans nidogen that acts with UNC-6 to establish the axon scaffold and the identification of a domain within UNC-6 (the C domain) that appears to inhibit axonal branching (branching occurs when this domain is deleted in an UNC-6deltaC construct). The goals of this application are 1) to determine activities associated with other structural modules in UNC-6; 2) to characterize suppressors of UNC-6deltaC; 3) to characterize two other genes that were identified in the screen that identified the C. elegans nidogen; and 4) to identify genes that are required for nidogen to position longitudinal nerves.
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