Worm Breeder's Gazette 10(2): 121
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 products of three genes, unc-5, a reciprocal pair of adhesive gradients on the hypodermis that guide migratory cells and pioneer neurons dorsalward or ventralward, respectively (1987 CSH Meeting Abstracts, p. 73). In particular, unc- 5 recessive mutations disrupt dorsalward migrations, unc 40 mutations primarily disrupt ventralward migrations, and unc-6 mutations disrupt migrations in either direction. The unc-5 and unc-6 genes have been recently cloned and their partial sequences are described in this issue (Leung-Hagesteign et. al., Ishii et. al.). If the unc-5, interact it might be expected that some mutations in these genes could be phenotypically suppressed by compensatory mutations in other members. Moreover, if these genes do encode adhesive molecules, then extragenic suppressors of unc 5, unc-6, or unc-40 mutations might also identify genes which encode their receptors on migratory cells or growth cones. Finally, partial loss-of-function mutations, particularly in the pleiotropic unc-6 gene, might identify functional domains within the guidance molecules. Here we describe several, apparently spontaneous, unc-6 mutations with unusual phenotypes and spontaneous unc-6 revertants, including an extragenic suppressor which maps to the unc-5 region of chromosome IV. In an effort to understand the functional organization of the unc-5, e isolated new uncoordinated mutants following treatment with the bacterial frameshift mutagen ICR- 191. As reported by other labs, this is not a potent mutagen in C. elegans; only 18 uncoordinated mutants were recovered from the progeny of approximately 100,000 treated Fl. Conceivably, some or all of these 18 strains represent spontaneous rather than induced mutations. Surprisingly, 4 of the 18 strains carried unc 6 mutations. The high proportion of unc-6 alleles in this small sample suggests that the unc- 6 gene is especially susceptible to ICR-191 or to spontaneous mutation. We believe the latter as we recovered 13 additional uncoordinated mutants in a screen of the progeny of approximately 50,000 unmutagenized F1. One of these spontaneous strains carried an unc-6 mutation (rh402). The behavioral and cellular phenotypes of two of these possibly spontaneous unc-6 mutants, rh201 and rh203, are indistinguishable from ev400, a null EMS-induced allele of unc-6 (see Table). Interestingly, the defects in the other three spontaneous unc-6 mutants, rh202, rh204, and rh402, are largely confined to dorsalward migrations. Thus these strains resemble e53, a null EMS-induced allele of unc-5. A fourth mutant with defects largely confined to dorsalward migrations, unc-6 ( rh69) following EMS treatment. Possibly all four of these dorsalward guidance defective alleles arose by a common, spontaneous mechanism rather than by chemical action. Three strains carrying unc-6 null mutations have reverted during laboratory passage. Two of these spontaneous revertants, unc-6 (rh46, ev436) and unc-6(ev400, ev437), represent intragenic events resulting in partial recovery of gene function. Interestingly, the ev437 mutation preferentially restores dorsalward guidance, leaving a residual phenotype similar to that of unc-40 recessive mutants. The third revertant, unc-6(rh83), V), carries a semi-dominant mutation which can partially suppress unc-6(rh83), but not unc-6(ev400). Preliminary mapping experiments have failed to separate sup (ev463) from unc-5. The frequent spontaneous loss or restoration of unc-6 gene function might be explained if this gene contains homologous domains which sometimes recombine unequally or convert one another. These repeated domains might be specialized for different functions, e.g., guiding dorsalward or ventralward migrations. It may be possible to separate sup (ev463) from unc-5 by genetic recombination or to prove its allelism to unc-5 by isolating new unc-5 mutations in the sup (ev463) background.