Genetic control of animal development

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

DESCRIPTION (provided by applicant): Our overall goal is to understand the mechanisms and principles underlying the robust control of cell division, cell fate, and morphogenesis during animal development. We employ the nematode worm Caenorhabditis elegans as a model for exploring how genetic regulatory networks produce precisely defined temporal and spatial patterns of cell fates regardless of changing physiological and environmental conditions. C. elegans is ideal for studying the genetic and molecular mechanisms for robust control of cell division and differentiation in animal development. This is because the temporal and spatial patterns of cell lineage development in C. elegans are essentially invariant across a broad range of growth conditions, including temperature, nutrient availability, and population density. To better understand this remarkably stress-robust development, we employ C. elegans developmental mutants that exhibit stress-sensitive phenotypes, and we use genetic and molecular analyses of these mutants to identify and characterize genetic regulatory mechanisms that buffer C. elegans development against stress. We particularly address how post-transcriptional gene regulation by microRNAs confers developmental and physiological robustness against environmental change. The expected outcomes of this study include a better understanding of, (from Aim 1) the robust coordination of gene expression programs in early animal embryos, (from Aims 1 and 2) developmental stability in the context of temperature stresses, and (from Aim 3) the global coordination of developmental rate and cell fate specification in the context of changing environmental resources. These outcomes promise to uncover fundamental principles relevant to human biology, including development, cancer, and tissue homeostasis and wound healing.