The proposed research is a continued investigation of the genetic control of development in a simple animal model. The approach is to apply genetic, microscopic, ultrastructural, molecular and biochemical methods to a detailed analysis of a postembryonic """"""""developmental switch"""""""" in the life cycle of the nematode, Caenorhabditis elegans. The switch is manifested at the second larval molt, when starvation or overcrowded conditions may result in the formation of the dauer larva, a developmentally arrested, non-feeding dispersal stage. Alternate developmental fates may be expressed (either formation of a growing third-stage larva, or formation of a dauer larva) based on environmental conditions. When the environment becomes favorable for growth, the dauer larva resumes feeding and development. The overall aim is to determine the genetic basis for the behavioral and developmental response to the environment, and the molecular and physiological mechanisms for implementation of the developmental program. Specific goals are proposed, which fall into complementary areas of investigation: (a) cloning and molecular characterization of selected genes involved in processing the response to environmental stimuli, (b) continued genetic studies, including the analysis of somatic mosaics to determine the developmental foci for action of specific genes that define steps in the genetic pathway for dauer larva formation, (c) electron microscopic and biochemical analysis of a mutant deficient in the synthesis of the dauer-inducing pheromone, (d) cloning and classification of sequences expressed specifically in animals destined to become dauer larvae, and not expressed in larvae committed to growth and (e) biochemical analysis of the physiological changes associated with entry into (and exit from) the dauer stage, including changes in protein phosphorylation. The analysis of wild-type developmental at the physiological level, and at the level of developmentally regulated gene transcripts, will provide new frames of reference for the analysis of mutant phenotypes. Finally, continued molecular characterization of dpy- 13 (""""""""dumpy""""""""), a collagen-like gene that effects body length, will be aimed at determining its role in specifying cuticle development and structure. It will be determined other dumpy genes are homologous to dpy-13.
Showing the most recent 10 out of 16 publications
