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 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 dauer larvae, a developmentally arrested, non-feeding larval stage. The overall aim is to determine the genetic basis of the developmental program for dauer larva formation and recovery, and the molecular and physiological mechanisms for the implementation of the developmental program. Specific goals are proposed which fall into six complementary areas of investigation: (a) biochemical and physical analysis of the biologically active substances, including a newly discovered pheromone, which act as environmental cues influencing the decision made between the two alternate developmental pathways, (b) selection and genetic analysis of mutants, either affected in the developmental decision preceding the L2 molt, affected in the timing of the developmental sequence leading to the dauer larvae, or affected in specific aspects of dauer larva morphogenesis, (c) electron microscopic characterization of the sensory neuroanatomy, or glandular anatomy, of specific mutants suspected to have sensory defects or secretory abnormalities, (d) developmental studies designed to test the response of developing larvae to specific environmental stimuli, and determine the timing of commitment to that to that response, (e) neurological studies designed to identify the specific cells which function in the process of entry into, or exit from, the dauer stage, and (f) molecular studies to determine the extent and timing of transcriptional controls associated with the alternate developmental sequences. New methods will be used to simplify genetic selection, and permit more rapid genetic analysis of mutants. The analysis of wild-type development 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.
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