We are interested in the molecules that are involved in nervous system development. In particular, we want to understand the molecular interactions that guide the growth cones of the axons of pioneer motor neurons. One guidance cue involved in guidance of axons is the UNC-6/Netrin ligand and it has two receptors UNC-40/DCC/Frazzled and UNC-5. These proteins are involved in the dorsal-ward guidance of the DA and DB motor neurons in C. elegans and the axons are misguided in mutant backgrounds. However, the absence of the cue and its receptors still allows the axons to migrate part-way towards the dorsal cord. This suggests the existence of at least one parallel genetic pathway involved in guidance of these neurons. We intend to identify the genes involved in this parallel pathway and have approached the problem by performing a genetic enhancer screen. We have conducted EMS screens on a strain containing
unc-129::gfp in an
unc-5(
e53) background to find mutants where the DA or the DB axons fail to leave their cell bodies in the ventral cord. We have thus far identified three such mutants. One of them is called YZ 1
(rq1) and we have mapped the gene on the genome and performed phenotypic analysis on the mutant strain. Currently, we are able to rescue the axon guidance defects and other phenotypic defects of
rq1 following cosmid microinjection. We are also able to phenocopy some of the defects using RNAi. Using forward and reverse genetics we are now close to the identification of the gene mutated in the first of our mutant strains.