We reported previously the characterization of 7 dominant vulvaless ( Vul) mutations, isolated as dominant suppressors of a
lin-16 multivulva (Muv) mutation [WBG 10 (3): 132]. These mutations, six of which are recessive lethal, were found to be alleles of
let-60, previously identified by recessive lethal alleles [Clark et al., Genetics, 119: 345 (1988)]. We refer to these semi-dominant alleles as
let-60(sd). The conclusions from our further studies on
let-60 can be summarized as follows.
let-60 and
lin-34 are likely to be the same gene.
let-60(sd) alleles were mapped between
dpy-20 and the left break-point of nDf27.
lin-34, identified only by semi-dominant Muv mutations, maps between
dpy-20 and
let-60 (G. Beitel, G. Jongeward, per. comms; our data). Our mapping data suggest that both are about 0.01 mu to the left of
dpy-20. Also,
lin-34 suppresses in trans the
let-60(sd) Vul phenotype. In fact, we have isolated a
lin-34(sd) allele as a dominant suppressor of the dominant suppressor phenotype of
let-60(sd). More intriguingly, the lethality of some
let-60(sd) homozygotes can be maternally rescued by
lin-34/+.Vulvaless is a loss-of-function phenotype of
let-60. We have isolated two intragenic revertants of
let-60(sd) by reverting the dominant Vul or suppressor phenotype of
let-60(sd). These revertants and the three previously isolated alleles (Baillie's lab) are likely null mutations because they behave similar to Dfs in heterozygotes.
let-60(null)/let-60(sd) animals from a
lin-34/let-60(sd) mother show a more severe defect in vulval induction (0%) than
let-60(sd)/+ (57% for the allele used), indicating that Vul is a loss-of-function phenotype. Thus, because Df/+ has wildtype vulva,
let-60(sd) alleles are dominant negative mutations. The level of
let-60 activity controls VPCs fates. In
let-60(sd)/+ animals,
let-60 activity is lower than that in
let-60(null)/+, resulting in a Vul phenotype. We propose, in light of our argument that
lin-34(sd) are alleles of
let-60, that a
lin-34(sd) mutation results in elevation of
let-60 activity and consequently a gonad signal independent Muv phenotype. Thus, a high level of
let-60 activity specifies 1 or 2 while a low level specifies 3 . It is also conceivable that
lin-34(sd) may be mutations in a distinct gene located very close to
let-60, but nonetheless result in an increase of
let-60 activity. Genetic interactions of
let-60/lin-34 with other genes suggest its position in the vulval induction pathway. The following pathway was deduced from examination of double mutant phenotypes: [See Figure 1]