Lin-1 has both positive and negative functions in specifying multiple cell fates induced by Ras/MAP kinase signaling in C. elegans

Abstract

lin-1 encodes an ETS domain transcription factor that functions downstream of a Ras/MAP kinase pathway mediating induction of the 1° cell fate during vulval development in the C. elegans hermaphrodite. Mutants lacking lin-1 activity display a phenotype similar to that caused by mutations that constitutively activate let-60 Ras consistent with a model in which lin-1 is a repressor of the 1° fate whose activity is inhibited by phosphorylation by MPK-1 MAP kinase. Here, we show that, contrary the current model, lin-1 is required positively for the proper expression of several genes regulated by the pathway in cells adopting the 1° cell fate. We show that the positive requirement for lin-1 is downstream of let-60 Ras and mpk-1 MAP kinase, and that it has a focus in the vulval precursor cells themselves. lin-1 alleles encoding proteins lacking a docking site for MPK-1 MAP kinase are defective in the positive function. We also show that lin-1 apparently has both positive and negative functions during the specification of the fates of other cells in the worm requiring Ras/MAP kinase signaling.