Worm Breeder's Gazette 7(2): 41
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.
In a previous Newsletter [6(1): 40, 1981], we described several classes of mutations affecting vulva development that mapped to the lin-12 III locus. We have continued characterizing these and other lin-12 mutations genetically and anatomically. We now think that lin- 12 acts as a binary switch during development to determine the expression of alternative cell fates in a number of different tissues. The studies of Sulston and White (1980) and Kimble (1981) have shown that, although laser ablation of most cells does not affect the fates of other cells, in a few cases the ablated cell is replaced, i.e. a neighboring cell (which normally adopts the '2 fate') adopts the fate of the ablated cell ('1 fate'). Because cells that normally adopt the 2 fate have the potential to adopt the 1 fate, such cells are considered to belong to an 'equivalence group.' That cell fate is altered after laser ablation implies that interactions among the cells of an equivalence group define the normal developmental program. Presumably these interactions affect the expression of genes that determine cell fate. We think that lin-12 is one such gene. Mutations in lin-12 affect the fates of the cells of the gonadal and ventral hypodermal equivalence groups; the mesoderm is similarly affected, suggesting that certain M cell progeny may be members of an equivalence group. We have examined the effects of three different classes of lin-12 mutations on these tissues. Two of these classes, lin-12(Muv) and lin-12(Vul), comprise semidominant mutations that by genetic criteria appear to result in the expression of elevated levels of lin-12 activity. One class, lin-12(0), comprises recessive, putative null alleles that lack lin-12 activity. The semidominant mutations result in discrete transformations that are opposite to the transformations caused by the lin-12(n) alleles, as shown in the table below. [See Figure 1] We described most of the semidominant alleles of the lin-12(Muv) and lin-12(Vul) classes in the previous Newsletter. Hermaphrodites that are homozygous or heterozygous for lin-12(Muv) alleles (n137, n177, and n427) have a multivulva phenotype resulting from the abnormal divisions of the cells of the vulval equivalence group. Note that these cell divisions are anchor cell (ac)-independent in lin-12(Muv) mutants; in wild-type hermaphrodites, the required for the induction of vulval cell divisions (Kimble, 1981). In lin-12(Vul) mutants (n379, n302, and n676), some ac-independent Pn.p cell ac is divisions occur but the alleles differ with respect to the frequency and extent of divisions; the most severe allele is n676, which as a heterozygote is generally vulvaless but as a homozygote shares some characteristics of the lin-12(Muv) mutants. For the gonadal and ventral hypodermal equivalence groups, it appears that the extreme semidominant mutations [the lin-12(Muv) class] result in the transformation of cells to the 2 fate. We have generated over 40 lin-12(0) alleles by reversion of n137, n302, and n676. Viewed through the dissecting microscope, some lin-12( 0) animals appear very scrawny, but others are of relatively normal size: hermaphrodites are sterile and have a large protrusion in the normal vulval position (they often explode as young adults), and males have abnormal tails. The lin-12(0) alleles in both the hermaphrodite and male result in the transformation of cells of the gonadal equivalence group to the 1 fate. The cell fates of the ventral hypodermal precursor cells indicate that the absence of lin-12 activity need not result in the expression of the 1 fate. In the ventral hypodermal equivalence groups, the three fates--1 , 2 , and 3 - -can be distinguished based on cell lineages. The fate of P9.p in lin- 12(0) males is 3 , not 1 . The hermaphrodite P(3,4,8).p cells, although variable, also demonstrate this point. By examining various heterozygous combinations of lin-12 mutations for the number of pseudovulvae and the frequency of functional vulva formation, we have inferred that the semidominant alleles result in the ectopic expression of lin-12. We can rank the various classes of alleles, by order of decreasing degree of ectopic expression, as lin- 12(Muv)> l)> > . Within the lin-12(Vul) class, we can rank the alleles as n676> n302> n379. We postulate that in wild-type development, cell-cell interactions result in the expression of a high level of lin-12 in certain cells, causing them to adopt the 2 cell fate. In other members of the equivalence group, we would expect the level of lin-12 activity to be low. In the gonadal equivalence groups, this low level of activity appears to be sufficient to result in the expression of the 1 fate. However, a low level of lin-12 activity is not sufficient for expression of the 1 fate in the ventral hypodermis, implying that other genes affect the determination of cell fate in this tissue.