Loss-of-function mutations in the neurogenic loci of Drosophila melanogaster lead to hypertrophy of the nervous system and reduction of the amount of epidermis formed by altering the pattern of embryonic cellular commitment: ectodermal stem cells which would normally enter the epidermal cell population are recruited into the neural cell population. A molecular genetic analysis of Delta, a member of the neurogenic gene set, is being undertaken in order to achieve an understanding of the function and regulation of Delta during embryogenesis and neurogenesis. Transmission genetics and morphological analysis will be employed to identify and characterize loci encoding products which interact with neurogenic gene products, to define the genetic and functional structure of Delta and to investigate the interactions among neurogenic genes. Recombinant DNA techniques will be employed to define the physical organization of the locus and the primary amino acid sequence of the Delta gene product(s) in order to test hypotheses concerning the function of the Delta gene product. Molecular probes for the transcriptional and translational products of Delta will be utilized to define the wild type spatial and temporal patterns of Delta expression, assess the impact of specific intragenic lesions on Delta expression, and determine the effects of other neurogenic loci, as well as interacting loci, on patterns of Delta expression. Elucidation of Delta function will be approached using germ line transformation of normal and aberrantly structured or regulated versions of the Delta locus and biochemical analysis of the Delta product(s) expressed in Drosophila tissue culture cells. Analysis of Delta presents an opportunity to elucidate molecular and genetic mechanisms by which products of specific genes regulate specific decisions during mechanism by which products of specific genes regulate specific decisions during embryogenesis and neurogenesis. Determination of Delta function and characterization of neurogenic gene interactions will enhance our understanding of mechanisms of cell-cell communication intrinsic to developmental processes, as well as the relationship between alterations in neurogenic gene expression and abnormal development of the nervous system. The results of these studies, to the extent they shed light on the relationship between ectodermal stem cells and precursor populations to the epidermis and nervous system, may prove useful in the development of cell replacement therapies for the treatment of developmental or externally induced neurological defects.

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National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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Indiana University Bloomington
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Shalaby, Nevine A; Parks, Annette L; Morreale, Eric J et al. (2009) A screen for modifiers of notch signaling uncovers Amun, a protein with a critical role in sensory organ development. Genetics 182:1061-76
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