In wild-type hermaphrodites, three of six Pn.p cells are induced to divide and generate vulval cells by a signal from the anchor cell. Fewer cells are induced in most worms carrying Vulvaless (Vul) mutations such as
let-23(syl), 53,
sy2,
el309) and
lin-7(
el413,
n760). However, the alleles
let-23(nlO45), 8, nlO5,
nl67) and
lin-7(
n308,
n701) result in a hyperinduced (Hin) phenotype. Specifically, worms homozygous for any one of these mutations average more than three Pn.p cells induced. This hyperinduction correlates with 'blips' near the vulva in egg- laying proficient (Egl+) worms. For
let-23(nlO45), this seems to be caused by a slight decrease of
let-23 activity [see Aroian and Sternberg, WBG 10(2)]. This hypothesis is based on the observations that nlO45/Df is tightly Vul and that a Hin phenotype can be recreated in a
let-23(syl)/1et-23
(mn224) heterozygote. (syl is a Vul non-lethal allele while
mn224 is a lethal allele which partially complements the Vul defect). Of these heterozygotes, 20% are Hyperinduced and 80% are wild type. According to the current hypothesis, this lower activity is sufficient to respond to the inductive signal but not capable of in turn activating the 'Lateral Inhibitory Signal' [Sternberg WBG10(1)] which prevents more than three cells from responding to the signal. To further examine this hypothesis, we have examined the interactions between Hin alleles of
let-23, tructed a set of double mutant strains carrying two Hin mutations. If the Hin phenotype of these strains is due to a lower level of activity, then a Hin; Hin double is predicted to have a Vul phenotype. Alternatively, if Hin is due to a heightened response to the inductive signal, then the double mutants should display a more extreme phenotype. As internal controls, we also constructed Hin; Vul doubles and Vul; Vul doubles. These strains also allowed us to determine whether there are any gene-specific or allele-specific interactions. As a measure of the level of induction, we have scored the number of Egl+ worms with one or more blips near the vulva divided by the total number of worms. For instance, a lineage such as 322123 or 332122 would be Egl+ with a blip, 322122 Egl+ with two blips (1, 2, and 3 refer to the primary, secondary and tertiary lineages; the underlined cells would form the vulva). The lineage 321123 is wild type at the plate level. This measure could also include some Vul animals with lineages such as 331323. Using this test,
let-23(nlO45) at 20 is 19% Hin,
lin-2(
n768) is 25%, and
lin-7(
n308) is 12%. We have set 10% as an operational definition of Hin. Of the seven Hin; Hin doubles that have been scored the highest score was less than 3%. These observations support the hypothesis that Hin alleles are hypomorphic. [See Figure 1] We have observed allele-specific interactions between
lin-2 and lin- 7. Two of the three Hin alleles tested,
lin-2(
n105) and
lin-2(
n768) decrease the penetrance of Vul alleles
lin-7(
e1413) and
lin-7(
n760), but the Hin allele
lin-2(
n167) does not suppress any of the Vul alleles tested. All of the other doubles are essentially Vul. We speculate that the
lin-2 and
lin-7 gene products interact directly. In addition, any double made with
let-23 (
n1045) is very tightly Egl- with little, if any, hyperinduction, consistent with the hypothesis that
let-23 acts at a different step than
lin-2 and
lin-7.[See Figure