ANALYSIS OF SENSORY NEURON DEVELOPMENT

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Our long term objectives are to understand the genetic control of cell differentiation in the Drosophila nervous system. The general strategy is to focus on one early differentiative step in Drosophila neural development, the segregation of sensory neurons. During segregation, postmitotic sensory neurons constrict apically and move out of the epidermal layer in which they were born. Using a developmental and molecular-genetic approach, we want to characterize genes which have an impact on this process. The specific objectives of this proposal are (1) to analyze the cellular mechanisms which underly sensory neuron segregation in wildtype development, and (2) to study the faint sausage (fas) gene which appears to be essential for neuronal segregation, as sensory neurons fail to segregate in homozygous fas- embryos. With regard to the first objective the following experiments are proposed: By blocking the function of microtubules, microfilaments, and cell adhesion (Ca++-dependent; integrin mediated) in an in vivo system it will be tested whether these functions are essential for sensory neuron segregation. It will further be asked whether mutations in genes implied in cell adhesion mechanisms (mys, 1(2)gl, fat) affect sensory neuron development. The study of the fas gene involves the analysis of ultrastructural defects in sensory neuron segregation in fas-embryos, fas-embryos derived from homozygous fas-eggs (germline clones), and clones of homozygous fas-cells in the adult epidermis. Birthdates and lineage relationships of the sensillum cells in fas-embryos will be determined. The fas locus will be mapped by recombination and deficiency mapping. The fas gene will be cloned and characterized by sequence analysis, in situ hybridization studies, and antibodies raised against the fas gene product. As fas appears to encode an essential factor for sensory neuron segregation, the molecular analysis will provide insight into the genetic control of this process.