The nematode Caenorhabditis elegans is a choice model system for study of the genetic control of development. The invariant somatic cell lineage provides an extremely precise mode of development for genetic dissection of the generation of specific cell types in prescribed positions at the level of individual cells. Two problems will be addressed. How are the details of specific lineage trees specified? And how is a specific lineage tree selected? A model based on current evidence for cell lineage controls will provide an intellectual framework for asking the first question. The choice of a lineage by sex, relying on the prior identification of a few genes critical to sex determination, will be used to address the second question. In addition, a genetic analysis of the control of the germ cell decision between mitosis and meiosis will be initiated. The cellular basis of this germ cell control, known uniquely in C. elegans, provides the foundation for embarking on this project. The bulk of this proposal involves the isolation and characterization of mutants in these developmental controls. A second part of this proposal focuses on development of the technique of microinjection into the developing worm. A link between genetics and biochemical analysis of identified genes is the ultimate goal of this project. Fluorescent tracer molecules will be injected to learn visually the fate of injected molecules. In vivo suppression by injection of a homologous amber suppressor tRNA will be used to test the function of an injected nucleic acid. Isolation of a stable plasmid will be attempted to use as a vector in future studies designed to introduce DNA into the organism. My long range objective is to elucidate the cellular and molecular control mechanisms that are responsible for fundamental decisions in development. The health relatedness of this work derives from its contribution to a more thorough understanding of basic mechanisms of cellular growth and differentiation controls. Defects in these controls may lead to congenital defects and to cancer in humans.
