Hedgecock 96-04145 The life history of an animal describes the sequence of global developmental stages from egg to adult. The most dramatic event is the transition from embryonic to larval development. Larval organ systems undergo coordinated growth and possibly remodeling at specific stages. The adult stage itself may have early and late components associated with reproductive senescence or increased mortality. Dr. Hedgecock proposes to characterize a novel family of nuclear receptor genes, designated ESCKA, implicated in life history regulation. Endocrine tissues secrete long-range chemical signals, or hormones, to coordinate development over large regions. Many hormones, typically steroids or other lipophilic molecules, act through an ancient family of proteins called nuclear receptors. In the model Caenorhabditis elegans, which is a nonparasitic nematode, the ESCKA receptor gene daf-12 is required to coordinate development of the entire organism at specific life stage transitions. He believes the proteins made by this gene, plus two other ESCKA genes discovered in this organism, provide tissues throughout the animal with a means of 'remembering" their current developmental age. Moreover, hormonal activation of these nuclear hormone receptors may allow these diverse cells to advance in unison to new stages in the nematode life history. Interesting, at least one ESCKA gene has been identified in insects, suggesting this family of nuclear receptors can tell us about life history regulation in all higher animals.
