PI: Mellerick-Dressler IBN: 9604413 The central nervous system (CNS) of both vertebrates and flies is composed of thousands of nerve cells, or neurons, each uniquely positioned, that express a specific combination of neurotransmitters and ion channels, and make appropriate contact with other neurons and target cells. The aim of this research is to understand how individual cell identities are specified during nervous system development. Because of the complexity inherent in mammalian nervous system development defined by both cell numbers and cell types, CNS specification is being studied in the fruit fly, Drosophila melanogaster, in Dr. Mellerick-Dressler's laboratory. Although relatively simple, Drosophila has proven to be an elegant and highly relevant model for analyzing gene function. The primordium of the nervous system is patterned along both the dorsal-ventral axis and the anterior-posterior axis by a variety of genes that regulate gene expression. One of these genes, called ventral nervous system defective (vnd) or NK-2, is expressed in a restricted dorsal-ventral population of cells that give rise to neurons in both fly and mammalian embryos suggesting that this gene family directs patterning. Indeed, fly embryos die and the central nervous system develops abnormally when mutations are present in the vnd/NK-2 gene, indicating that this gene is critical for neural development. To test the hypothesis that vnd/NK-2 functions in neuronal patterning, existing vnd/NK-2 mutants will be examined for altered expression of genes that are normally expressed within the vnd/NK-2 expression domain. The functional significance of the temporal and spatially restricted pattern of vnd/NK-2 gene expression will be addressed by generating and analyzing two different types of genetically altered "transgenic" fly embryos -- one that expresses vnd/NK-2 in all cells, the second that over-expresses the gene within a restricted population of cells during CNS development. Finally, with the even tual aim of addressing whether expression of vnd/NK-2 is functionally significant after embryogenesis, the temporal and spatial localization of the vnd/NK-2 gene product will be determined in wild-type flies after embryonic CNS development. The working hypothesis underlying this research is that many aspects of vnd/NK-2 function and regulation are evolutionarily conserved. Thus, the results from this work may also contribute to understanding how vertebrate vnd/NK-2 like genes function during neural development.
