Novel heterochronic functions of the Caenorhabditis elegans period-related protein LIN-42

Abstract: LIN-42, the Caenorhabditis elegans homolog of the Period (Per) family of circadian rhythm proteins, functions as a member of the heterochronic pathway, regulating temporal cell identities. We demonstrate that lin-42 acts broadly, timing developmental events in the gonad, vulva, and sex myoblasts, in addition to its well-established role in timing terminal differentiation of the hypodermis. In the vulva, sex myoblasts, and hypodermis, lin-42 activity prevents stage-specific cell division patterns from occurring too early. This general function of timing stage-appropriate cell division patterns is shared by the majority of heterochronic genes; their mutation temporally alters stage-specific division patterns. In contrast, lin-42 function in timing gonad morphogenesis is unique among the known heterochronic genes: inactivation of lin-42 causes the elongating gonad arms to reflex too early, a phenotype which implicates lin-42 in temporal regulation of cell migration. Three additional isoforms of lin-42 are identified that expand our view of the lin-42 locus and significantly extend the homology between LIN-42 and other PER family members. We show that, similar to PER proteins, LIN-42 has a dynamic expression pattern; its levels oscillate relative to the molts during postembryonic development. Transformation rescue studies indicate lin-42 is bipartite with respect to function. Intriguingly, the hallmark PAS domain is dispensable for LIN-42 function in transgenic animals. [Copyright &y& Elsevier]