The
vab-8 gene of is necessary for posterior migrations of several cells and axons in C. elegans. One class of
vab-8 mutants show defects in the posterior migration of the CAN neuron and in the posterior extension of the AVA, AVB, AVD, and AVK axons, while a second class of mutants are defective only in the extension of these axons (1). We have found that the sequence of genomic and cDNA clones predicts that
vab-8 encodes two proteins of 1066 and 541 amino acids. The larger protein is distantly related to kinesin: it has a kinesin-like motor domain at its N-terminus, a central region with a predicted coiled-coil structure, and a globular C-terminus. The mRNA for the smaller protein is initiated at a distinct exon within an intron of the larger transcript. This smaller protein thus has a unique 29 amino acid N- terminus, but the remaining C-terminal 513 amino acids are identical between the two proteins. A DNA fragment encoding both proteins can rescue all the phenotypes of
vab-8 mutants, and a smaller fragment encoding the 541 amino acid protein can rescue the migration defect of the CAN cell but not the axon guidance defect. As inferred from lacZ fusions, the
vab-8 gene is expressed in the AVK and CAN neurons, and also in many other cell types whose function is not noticeably impaired in
vab-8 mutants, including body, pharynx, and vulval muscles; the developing vulva and spermatheca-uterine valve; and in the excretory cell. Fusions corresponding to the small transcript are expressed in the CAN neuron, while fusions corresponding to the large product are expressed in AVK but not CAN; these results are consistent with cell- autonomous function. Analysis of genetic mosaics indicates that wild-type
vab-8 product must be expressed in the CAN cells for them to migrate correctly. These results, together with previous phenotypic analyses, suggest that
vab-8 encodes a novel motor protein that functions in orientation of cells as a prelude to cell or axon migration. Wightman et al. (1996). The C. elegans gene
vab-8 guides posteriorly directed axon outgrowth and cell migration. Development 122, 671-682.