Worm Breeder's Gazette 13(3): 89 (June 1, 1994)

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.

unc-107 / vab-8 mutants are defective in posterior-directed axonal outgrowth and cell migration

Bruce Wightman[1], Scott Clark[2], Anna Taskar[1], Wayne Forrester[1], Villu Maricq[2], Jen Zallen[2], Con Bargmann[2], Gian Garriga[1]

[1]Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720
[2]Department of Anatomy, University of California, San Francisco, CA, 94143

We are interested in the mechanisms that guide axons and migrating cells to their targets. Both unc-107 ( ev411 )and vab-8 ( e1017 )mutants are defective in outgrowth of a number of axons that grow from anterior to posterior. Defective axons are variably shortened, usually terminating at positions well anterior of their normal destinations. AVA, AVB, AVD, AVK, ALA, CAN, and PDE all have shortened posterior-directed axons in both mutants. In addition to these axons, the posterior arm of the excretory canal is also shortened. Because the affected axons and cellular processes extend along both the ventral cord and lateral body wall, the defect does not seem to be limited to growth on a particular substrate. Of the posterior-directed axons examined only RID, which grows along the dorsal cord, is not shortened in either mutant.

In contrast, many dorsal, ventral, and anterior-directed axons are not shortened in either unc-107 ( ev411 )or vab-8 ( e1017 )mutants. Dorsal-directed outgrowth of the DDn and VDn axons and ventral-directed outgrowth of the HSN, PDE, RMG, and ADE axons are normal in both mutants. Anterior-directed axons of HSN, PDE, PVC, and CAN are not shortened in either mutant. The observation that anterior-directed axons of PDE and CAN are not shortened, while posterior-directed axons from the same neurons are shortened, indicates that the mutations do not affect the process of axonal outgrowth in general, but rather affect outgrowth only in the posterior direction. There are two exceptions: PHA and PHB, both of which have shortened anterior-directed axons.

vab-8 mutations also disrupt posterior-directed cell migration. Some cells that migrate from anterior to posterior stop short of their normal destinations (CAN, ALM, and the coelomocytes), while cells that migrate from posterior to anterior reach their destinations (HSN). Dorsal migrations of the distal tip cells are not affected, but posterior-directed migrations are defective. Again, there are exceptions: the posterior-directed migrations of Z1 , Z4 ,and M are not significantly affected (1). In unc-107 mutants, the ALM and distal tip cell migrations are defective, but CAN, HSN, and coelomocyte migrations are normal.

We have mapped unc-107 between sma-1 and myo-3 on chromosome V, suspiciously near vab-8 .An array containing pooled cosmids from this region, created by David Hsu, rescues unc-107 ( ev411 ).Ming-Shiu Hung and Jeff Way have shown that one of the cosmids in this pool, C35G11 ,rescues vab-8 ( e1017 )mutants (2). We have found that C35G11 also rescues unc-107 ( ev411 )mutants. Furthermore, 82% of unc-107 ( ev411 )/ vab-8 ( e1017 )trans-heterozygotes are uncoordinated, while 18% exhibit nearly wild-type movement. A small percentage (9%) are both Unc and PVul (protruding vulva), a phenotype associated with e1017 but not ev411 .None of the ev411 / e1017 trans-heterozygotes exhibited the withered tail characteristic of homozygous vab-8 mutants. Therefore, ev411 and e1017 fail to complement for the Unc phenotype associated with both mutations, but complement for the withered tail phenotype. Based on these data, and the similar anatomical phenotypes discussed above, we believe that ev411 and e1017 are mutations in the same gene, and that ev411 is a weaker allele.

We postulate that the unc-107 / vab-8 complementation group may play a role in the production or interpretation of an anterior-posterior patterning signal used by some migrating cells and outgrowing axons during nematode development. We are currently undertaking genetic and molecular approaches to test this model.

Literature Cited:

(1) Manser and Wood (1990) Developmental Genetics, 11:49-64 .

(2) Personal communication