Worms depend on taste, touch and smell to sense and explore their environment. Appropriate responses to information received through these different modalities depend on precise connectivity between sensory neurons and downstream effector neurons in the nerve ring. Little is known about how axons migrate through the nerve ring neuropil during development to find their synaptic partners. Chemosensory axon development can be divided into four stages of growth: 1) initial ventral outgrowth in the amphid commissure (which includes outgrowth and ventral guidance), 2) axons join the nerve ring, 3) dorsal extension in nerve ring, 4) target identification and termination. To study this process 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 ( s ensory ax on guidance). We have isolated five alleles of
sax-10 . The canonical allele,
ky297 , has defects in both sensory axons and interneuron axons in the nerve ring. Many classes of axons reach the nerve ring appropriately, but then terminate or become misguided. Axons in the body and ventral cord appear normal. A subset of sensory axons are misguided or terminated in
sax-12 mutants, suggesting a more specific defect.
sax-13 also affects many but not all sensory axons and some interneurons in the nerve ring. Despite these defects the overall position and morphology of the nerve ring is normal in many
sax-10 ,
sax-12 and
sax-13 animals.
sax-14 , however, has more severe nerve ring phenotypes that are being characterized further. Mutations in
sax-10 ,
sax-12 ,
sax-13 , sax
(ky353),
sax-5 ,
sax-3 ,
unc-6 and
unc-40 affect the dorsal extension of axons and may play a role in pathfinding. Mutations in
sax-12 ,
sax-13 ,
sax-5 ,
sax-3 ,
unc-6 and
vab-1 also affect the first guidance step, initial ventral guidance, of some chemosensory neurons. 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. We will present our latest progress in these endeavors.