C.elegans morphogenesis is a complex process requiring numerous short-range migrations, rearrangements, and concerted cell movements. Several existing C.elegans mutants disrupt essential morphogenic events since they result in severe body deformities, classically described as a vab (variable-abnormal) phenotype. Several studies have demonstrated that molecules shown to play cell and axon guidance roles in other model systems have homologues in the worm that play broad roles in hypodermal morphogenesis (George et al., 1998, Cell 92, 633-643; Wang et al., 1999, submitted). For example,
mab-20 mutants that have disruptions in the C.elegans homologue of Drosophila Semaphorin II, have severe morphological deformities, axon guidance defects and fusion of sensory rays in the male tail. Ectopic hypodermal cell contacts and other observations in
mab-20 mutants suggest that Semaphorin II is required to repel cell extensions (Roy et al., 1999, in preparation). Another previously isolated mutant called
vab-6 has several phenotypic traits that are strikingly similar to those observed in
mab-20 mutants, including ectopic hypodermal seam cell contacts, male tail sensory ray fusions and misguided axons. Although
mab-20 and
vab-6 mutants may affect the same developmental events, a double mutant between a putative
mab-20 null mutation (
ev574) and
vab-6(
e697 ) could not be made on several attempts. This suggests that
mab-20 and
vab-6 may be in parallel pathways. Consistent with this hypothesis, double mutants containing a temperature sensitive allele of
mab-20(
bx61) (Baird et al., 1991, Dev. 113, 515-526) and
vab-6(
e697) display embryonic lethality and severe morphological defects at restrictive temperatures.
vab-6 genetically maps to position -27.17 on LGIII near
unc-45 (-27.13) (Dave Pilgrim, personal communication). To better understand the function of VAB-6, we are presently trying to clone the gene. We show that the morphological abnormalities of
vab-6 can be rescued with the cosmid F10C5 that resides to the left of
unc-45 . F10C5.2 is a predicted transmembrane protein and F10C5.1 has a region highly homologous to the TPR domains found in yeast CDC16, CDC23 and CDC27. We are now trying to identify a smaller rescuing DNA fragment within that cosmid.