Characterization of the class A synthetic Multivulva genes, which act in C. elegans vulval development

Abstract

The class A and B synthetic Multivulva (synMuv) genes function redundantly to inhibit Ras-mediated vulval development in C. elegans. The class B synMuv genes encode an Rb/DP/E2F repressor complex that likely silences genes required for vulval specification through chromatin modification and remodeling. Rb has been extensively characterized as a tumor suppressor gene in mammals. Of the four known class A synMuv genes, only the lin-15A locus was cloned previously and encodes a novel protein. To further our understanding both of the mechanism by which the synMuv A genes inhibit vulval induction and of the nature of their functional redundancy with Rb, we have cloned and characterized additional members of this pathway. We find that the class A synMuv gene lin-56 encodes a novel nuclear protein that shares an atypical CCCH motif with the class A synMuv protein LIN-15A. LIN-56 and LIN-15A depend on each other for wild-type protein levels. We propose that LIN-56 and LIN-15A normally associate in a functional complex required for vulval fate inhibition, and that complex formation is essential for the stability of both proteins. We find that a third class A synMuv gene, lin-8, is the defining member of a large and novel C. elegans gene family. The LIN-8 protein is also nuclear and interacts with the product of the class B synMuv gene lin-35, the C. elegans homologue of mammalian Rb. This is the first report of a direct molecular interaction between the class A and B synMuv pathways. Our data support a model in which the class A synMuv genes function in transcriptional regulation.