A strawberry notch homolog, let-765/nsh-1, positively regulates lin-3/egf expression to promote RAS-dependent vulval induction in C. elegans.
The specification and patterning of vulval precursor cells (VPCs) in Caenorhabditiselegans is achieved using a conserved EGFR/RAS signaling pathway that is activated by the ligand lin-3/EGF, which is secreted by the neighboring somatic gonad. Previous work has demonstrated that the expression of lin-3 must be tightly regulated to ensure that only three of six equivalent VPCs are induced to differentiate into the mature vulva. Here, we have identified a novel regulator of EGFR/RAS signaling, let-765/nsh-1, that functions upstream of the pathway to promote vulval induction. let-765 encodes a conserved DExD/H box helicase protein and is the C. elegans ortholog of Drosophila strawberry notch. By investigating genetic interactions between let-765 and RAS pathway genes as well as with synthetic multivulva (synMuv) genes, we have demonstrated that let-765 positively regulates the RAS pathway and antagonizes synMuv activity at the level of lin-3/EGF. In support of these proposals, we found that LET-765 is required for producing wild-type levels of lin-3 mRNA. Mutations in let-765 result in pleiotropic phenotypes that imply its function must be required in multiple developmental processes and, together with data presented here, suggest that LET-765 promotes the expression of diverse targets, potentially through interactions with transcriptional activator or repressor complexes.
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C., Canada. csimms@sfu.ca
Carrie L
CL
Simms
David L
DL
Baillie
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D014844:Vulva / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor