The C. elegans vulva is induced by an EGF like signal that activates the highly conserved Ras/MAPK pathway. Constitutively active alleles of ras lead to hyperactivity of the signal transduction pathway and result in a multivulva (Muv) phenotype where numerous pseudovulvae are formed from ectopically induced vulval precursor cells (VPCs). By initiating suppressor screens of activated
let-60 ras, many previously unknown components of this pathway have been identified. One suppressor,
ku258, is a semi-dominant mutation isolated in a screen for temperature sensitive mutations that suppress the
let-60(
n1046) allele. While homozygous
ku258 can suppress
let-60(
n1046) from 80% Muv to 5% Muv,
ku258/ + heterozygotes also suppresse the
let-60(
n1046) phenotype to 10% Muv. Additional genetic analysis, such as the ability of
ku258 to suppress the Muv phenotype of
lin-1(
e1275), has suggested that
ku258 acts at a late step in the Ras/MAPK signaling pathway. Interestingly,
ku258 is not able to suppress the muv phenotype caused by a
lin-31(lf) mutation. Animals carrying the
ku258 mutation are also semi-sterile, display lethality in 25% of their embryos and show defects in other developmental processes.
ku258 was fine mapped using single nucleotide polymorphisms (SNPs) to a 20 kb region on LGIII. A lesion corresponding to the
ku258 mutation was found in an open reading frame coding for the worm homolog of CBP/p300,
cbp-1. Further genetic, molecular and biochemical analysis is currently being performed to better understand the role of
cbp-1 in ras signaling and vulval induction.