During vulval development, three out of six vulval precursor cells (VPCs) are induced by a signal from the gonadal anchor cell (AC) to adopt vulval cell fates. The AC triggers vulval differentiation by activating a highly conserved RTK/RAS/MAP kinase pathway in the VPCs. C. elegans is attracted to certain volatile compounds such as isoamyalcohol, diacetyl or benzaldehyde. When animals are exposed to a volatile attractant, the RAS/MAP kinase pathway is activated in two pairs of chemosensory neurons (AWA and AWC) in the head (Hirotsu et al. (2000) Nature 404, 289-293). Furthermore, chemotaxis is compromised by mutations that perturb the activity of the RAS/MAP kinase pathway. We have performed genetic screens to identify negative regulators of RAS/MAP kinase signalling during vulval induction. While cloning one of these inhibitory genes (
meg-1 ), we have identified the
sml-1 gene (for sm el l ; ORF F49E12.5) because overexpression of
sml-1(+) efficiently rescues the
meg-1 multivulva (Muv) phenotype.
sml-1 encodes a seven-pass transmembrane protein similar to the sra family of chemosensory receptors. A SML-1::GFP fusion is expressed in the AWA and AWC chemosensory neurons, but no expression can be observed in the VPCs. We have isolated a
sml-1 deletion allele (
zh13) that removes most of the coding region.
sml-1(
zh13) single mutants exhibit slightly increased chemotaxis to isoamylalcohol or diacety but no obvious vulval defects. However, loss of
sml-1 function partially suppresses the chemotaxis defect of
let-60(
n2021) or
lin-45(
sy96) mutants and the vulvaless (Vul) phenotype of
let-60(
n2021),
let-60(
n2031 dn )/+ or
sem-5(
n2019) mutants. Thus, SML-1 acts antagonistically to the Ras/MAP kinase signalling pathway both during vulval induction and chemotaxis. Overexpression of
sml-1 under control of its own promoter (
sml-1(XS) ) causes several phenotypes, some of which can also be observed in starved animals.
sml-1(XS) animals are defective in chemotaxis to volatile attractants, they are weakly Vul, Unc, Egl and 14% of the animals enter the dauer stage at 25 o C. SML-1 function is in part mediated by the GPA-5 G protein-alpha subunit. A
gpa-5 loss-of-function mutation (Jansen et al. (1999), Nature Genetics 21:414-419) partially rescues the chemotaxis defect of
sml-1(XS) animals and it suppresses the
let-60(
n2021) chemotaxis and vulval defects. Interestingly, we observed that under limiting food conditions the Muv phenotype of
let-60(
n1046gf) decreases, while
sml-1(
zh13);
let-60 (1046gf) double mutants appear to be insensitive to food conditions. Thus, SML-1 may act as a sensor in the AWA and AWC neurons to regulate vulval induction in response to the external conditions.