vab-8 acts in posteriorly directed cell and axon growth cone migrations in a cell autonomous manner.
vab-8 functions in posterior ALM cell migration but not in later anterior ALM axon migration, and continuous
vab-8 expression in the ALM can reorient anterior ALM axon outgrowth posteriorly. This finding suggests that the direction of migration can be regulated at the level of
vab-8 activity.
vab-8 encodes two isoforms of a novel intracellular protein, and the opal null allele
e1017 is predicted to remove both activities. Our analysis of
vab-8 has led us to propose that there exists at least one mechanism for the global guidance of posterior migrations. To identify other genes that function in posterior guidance, we suppressed the highly penetrant CAN cell migration defect of
vab-8(
e1017) mutants. Extragenic suppressors could identify genes that act downstream of
vab-8 as well as genes that act in parallel pathways. From screening over 20,000 genomes we isolated four partially penetrant van (variably abnormal normal) suppressors, each defining a distinct gene.
van-1(
gm128) is a semi-dominant suppressor of
vab-8 cell and axon outgrowth defects that is allele non-specific but at least so far is gene specific. Alas,
van-1 has no phenotype on its own. In dosage studies
van-1(
gm128) appears to alter gene function. We have mapped
van-1 to LGI between
stu-4 and
unc-11 and transformation rescue experiments are underway.