Worms depend on taste, touch and smell to sense and explore their environment. Appropriate responses to information received through these different modalities depends on precise connectivity between sensory neurons and downstream effector neurons in the nerve ring. Little is known about how axons migrate through this nerve ring neuropil during development to find their partners. How is positional information interpreted by an extending axon so that desired synaptic partners are found? We focused on the guidance of the ASI chemosensory neurons to their appropriate positions in the nerve ring. A mutant screen led to the isolation of 16 candidate mutant strains that appeared to have ASI axon guidance and termination phenotypes. These mutations define at least five new genes which we have named
sax-10-14 (sensory axon guidance). We have isolated five alleles of
sax-10. The canonical allele,
ky297, has axon defects in several axons in the nerve ring including the chemosensory neurons AWB, ASI and ASH and the interneuron PVQ, as well as an altered expression pattern of the AWC- specific gene
str-2.
ky297 is normal for the VD, DD and HSN motoneurons, the chemosensory neuron ADL and the phasmids.
sax-12 suffers from defects in ASI and ADL, but is normal for AWC structure.
sax-13 displays abnormal axon structures when we examine ASI, ADL, AWB, ASH and PVQ, but appears wild-type for AWC. Mutants display either one or a combination of phenotypes (including: premature termination, branching, thickening, wandering and inappropriate pathfinding) with a penetrance that ranges from 13% to 100%. Dye filling of sensory neurons with the fluorescent dye DiI, and examination of neurons with other cell-specific GFP constructs in these mutants reveals that the overall morphology of the nerve ring is normal in many
sax-10,
sax-12, and
sax-13 animals, and that the mutations disrupting ASI are probably in genes specifically required by ASI or a subset of neurons.
sax-14, however, has more severe dye filling phenotypes that are being characterized further. To facilitate genetic analysis and cloning of these new sax genes, we are mapping the genes and currently trying to rescue the
sax-10 phenotype by cosmid injections and germline transformation.