The proposed research is concerned with the mechanisms underlying differential gene expression and pattern formation in eucaryotic development. Our study aims at the molecular characterization of genetic loci which affect the ectodermal differentiation in the very early embryo of Drosophila melanogaster. Genetic analysis has revealed that the early differentiation of the ectoderm into epidermal precursor cells and neuroblasts is under the genetic control of a small group of genes. The best characterized locus among this group is the Notch locus. Notch mutations fundamentally affect the differentiation of the ectoderm in the embryo by interfering in an unknown fashion with the normal developmental program, causing the hypertrophy of the nervous system. We initiated a molecular study of this developmentally significant locus in an attempt to gain insight into its biochemical nature and its mode of action during development. During the last two years we were able to isolate the DNA sequences which define the Notch locus, construct a physical map and correlated it to the genetic map, construct and analyse several new Notch alleles and define the transcriptional activity of the cloned sequences. This work has indicated the necessity for a more detailed analysis. We propose the continuation of the molecular characterization of the Notch locus by exploring in greater depth its structural features, its expression and mode of action during development and by isolating and characterizing the gene product.
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