Worm Breeder's Gazette 14(3): 58 (June 1, 1996)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

The C. elegans vab-8 gene encodes two kinesin-related proteins necessary for axon outgrowth and cell migration

Ming-shiu Hung1, Fred Wolf2, Bruce Wightman2, Gian Garriga2, Jeffrey C. Way1

1 Biol. Dept., Nelson Labs, Rutgers University, Piscataway, NJ 08855
2 Dept. of Molecular and Cell Biol., 401 Barker Hall, Univ. of California, Berkeley CA 94720

     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 the axons (1). We have found that the
sequence of genomic and cDNA clones predicts that vab-8 encodes two
proteins of 1066 and 582 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 553
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 582 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.