Proper nervous system function requires that developing neurons acquire specific identities and express appropriate cell-specific characteristics. The long term goal of the investigator is to understand the mechanisms underlying these processes. The principal investigator plans to investigate these mechanisms by studying development of individually identified primary motoneurons in embryonic zebrafish. The principal investigator proposes that the individual identities of primary motoneurons are specified by a series of signaling interactions that: i) specificy cells as primary motoneurons, ii) pattern the cells so they are located in specific spinal cord positions, iii) induce the cells in these different positions to express cell-specific genes that specify individual fates and iv) promote survival by providing trophic support. The principal investigator proposes to test whether primary motoneurons inhibit neighboring cells from becoming primary motoneurons and whether this inhibition is mediated by the """"""""neurogeneic """""""" proteins, Notch and Delta. By fate mapping the medial neural plate, the principal investigator will learn where primary motoneurons arise and the normal fates of their neighbors. By examining how the fate map is altered in mutants with excess primary motoneurons and in embryos ectopically expressing either native or dominant negative Delta proteins, the principal investigator will learn whether neurogenic genes pattern the arrangement of primary motoneurons. The principal investigator proposes to learn about signals that induce prospective primary motoneurons to express position-specific genes and adopt individual fates. The principal investigator will test the role of a candidate receptor to learn whether it induces expression of a gene specific for a particular mtoneuronal fate. The principal investigator will learn about other signals that regulate motoneuronal fates by isolating and characterizing mutations that alter the expression patterns of genes specific for several different motoneuronal fates. The principal investigator proposes to learn whether a specific motoneuron dies because signals from identified muscle cells prevent its axon from reaching a source of trophic support. Two identified motoneurons form an equivalence pair in which one survives and the other dies; death requires the presence of identified muscle cells. The principal investigator will examine mutants, transplant cells, and isolate potential signaling molecules to learn the nature of the interactions that cause this motoneuron to die and whether death results from lack of trophic support.
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