HES-Mediated Repression of Pten in Caenorhabditis elegans

摘要

The hairy/enhancer-of-split (HES) group of transcription factors controls embryonic development, often by acting downstream of the Notch signaling pathway; however, little is known about postembryonic roles of these proteins. In Caenorhabditis elegans, the six proteins that make up the family are considered to be HES orthologs that act in both Notch-dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the family works to coordinate postembryonic cellular events, we performed a functional characterization of the family member, . We show that, after embryogenesis, expression persists throughout every developmental stage, including dauer, into adulthood. Like animals that carry loss-of-function alleles in genes required for normal cell-cycle progression, the phenotypes of animals include reduced brood size, unfertilized oocytes, and abnormal gonad morphology. Using gene expression microarray, we show that the transcriptional network correlates with the phenotypes of animals and that the C. elegans Pten ortholog, , is one major hub in the network. Finally, we show that regulates C. elegans lifespan and dauer recovery, which correlates with a role in the transcriptional repression of activity. Collectively, these data provide the first genetic evidence that may be a functional ortholog of mammalian HES1, which represses PTEN activity in mice and human cells.