Neurogenic genes influence the earliest cellular commitments observed during embryonic ectodermal differentiation in Drosophila. Mutations affecting these loci can result in hypertrophy on the central nervous system, reduction in the amount of epidermis formed, and embryonic lethality. The cellular basis for this phenotype is recruitment into the neural cell population of ectodermal stem cells which would normally enter the epidermal cell population. Analysis of the neurogenic gene set presents a rare opportunity to elucidate the mechanism(s) by which products of specific genes regulate specific developmental decisions during embryogenesis and more specifically neurogenesis. Molecular cloning of Delta, one of the neurogenic genes, will be undertaken in order to define the physical structure of the locus in wild type and mutant animals by comparative DNA blot analysis. The genetic structure of the locus will also be investigated using the powerful tools of Drosophila genetics. Comparison of the physical and genetic structure of Delta will serve as the basis for understanding the relationship between the structure and function of a gene which regulates developmental decisions. Molecular probes will be employed to characterize temporal and spatial variation in Delta transcription during embryogenesis in wild type and mutant animals using RNA blot analysis and in situ hybridization to tissue sections of developing animals. Patterns of gene expression will be related to patterns of ectodermal differentiation. The use of germ line transformation will permit conclusive identification of chromosomal sequences encoding the Delta function. Genetic screens designed to identify loci which interact with Delta will also be initiated. Finally, the effect of other neurogenic genes on Delta expression will be analyzed to determine whether neurogenic genes interact at the level of transcription. The results of this experimental program will enhance our understanding of the molecular and genetic basis for the control of development, as well as the relationship between alterations in neurogenic gene expression and abnormal development of the nervous system.
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