Nutritional Control of Developmental Programs

Nutritional control of developmental programs

The long term goal of the proposed research is to elucidate the mechanism(s) by which nutritional cues are linked to the initiation of developmental programs in animals. This problem is fundamental to animal development, but has received relatively little attention at the molecular level. The simplicity of C. elegans and its ease of growth and manipulation makes it an ideal system for these studies. In particular, food availability during postembryonic development is simply controlled, and the worm's transparency allows developmental responses to food to be easily monitored. The proposal focuses on dissecting two genetic pathways: 1) a daf-18-mediated signaling pathway that actively controls the initiation of postembryonic development in response to food, and 2) the heterochronic gene pathway that times certain postembryonic events and is influenced by environmental conditions, including food availability. The presence of food initiates and coordinates timing of postembryonic developmental programs in diverse tissues of the worm. If nematodes are hatched in the absence of a food source, they arrest development. Work in the Rougvie laboratory indicates that DAF-18, the worm homolog of the tumor suppressor PTEN, is required for arrest of postembryonic developmental programs under starvation conditions. Components of the daf-18-mediated nutritional response pathway will be defined by testing candidate genes for involvement and by conducting genetic screens to identify novel components. Nutritional inputs also impinge upon the heterochronic gene pathway, but the mechanism by which these external signals influence timing genes is unknown. Temporal progression of postembryonic cell fates is triggered by the accumulation of the lin-4 microRNA which subsequently acts to down-regulate target genes. In the absence of food, lin-4 expression is not activated and development does not progress. In addition, another heterochronic gene, lin-42, is extremely sensitive to environmental conditions during development; its mutant phenotype is suppressed by adverse conditions. Genes will be identified that link environmental cues to the heterochronic gene pathway via lin-4 or lin-42. Broader impacts: This project will contribute to the training of a postdoctoral fellow, graduate and undergraduate students. Emphasis will be placed on developing testable hypotheses and critical interpretation of data. Past undergraduates in the laboratory have co-authored papers, and it is anticipated that undergraduate trainees supported with award will make similar contributions while conducting their research projects.