During the development of hermaphrodite vulva three out of six equivalent vulval precursor cells (P3.p to P8.p) in the ventral hypodermis are induced by the gonadal anchor cell (AC) to adopt vulval cell fates. The anchor cell signal activates in P6.p the conserved EGFR/RAS/MAPK pathway that specifies the primary cell fate. A lateral signal from P6.p then activates the LIN-12/NOTCH signaling pathway in P5.p and P7.p that regulates the secondary cell fate. Hyper-activation of the RAS/MAPK pathway leads to multivulva (Muv) animals, while inactivation of the pathway results vulvaless (Vul) phenotype. Though the EGFR/RAS/MAPK pathway has been extensively studied in many organisms, less is known about the proteins that negatively regulate it. One known negative regulator is the RAS GTP-activating protein GAP-1. Although
gap-1(0) animals do not exhibit vulval phenotype as single mutants, they show a multivulva phenotype a sign for RAS/MAPK hyper-activation together with mutations in other negative regulators. In order to identify more negative regulators of the RAS/MAPK pathway we performed an EMS mutagenesis screen in a
gap-1(0) background and selected for multivulva animals in the F2 generation. One of the mutations we isolated,
ga139 shows an 80-100 % multivulva phenotype in a
gap-1(0) background and partial sterility.
ga139 maps to the left arm of chromosome I between the SNPs Y37E3.3 and Y39G10AL.1, covering a 100 kb region with nine candidate genes. Currently rescue experiments and sequencing is being carried out to identify the gene in
ga139 animals.