The studies proposed here will provide a phenotypic and molecular characterization of the facet mutations of drosophila. These mutations, which map to the well studied notch locus, affect development of the eye. Preliminary data indicate that these mutations alter non-coding regions of the notch transcript, thereby suggesting the possibility that the mutations are regulatory, rather than structural. This is consistent with the observation that other notch mutations affect a well defined step in neurogenesis in the early embryo, rather than morphogenesis of the eye. The eye defects caused by facet mutations are less well described; the ultrastructural analysis proposed here should increase our understanding of the relationship of the two different phenotypes associated with mutations at the notch locus. Additional proposed experimentation will identify other genes that play a direct role in controlling the expression of notch, or in the function of its product. One of the central aims of modern biology is to provide an understanding of the mechanisms that control development of multicellular organisms. Study of drosophila has been one of the most important approaches to this problem, in part because of the powerful genetic analysis possible with this organism. A number of mutations which affect cellular differentiation in drosophila are known; among these, mutations at the notch locus have been shown to affect the decision of certain cells in the early embryo to form either neural or epidermal tissue. Remarkably, some notch mutations, called facet mutations, instead cause defects in the eye. The proposed experiments will provide a careful analysis of these eye defects, which have not been well characterized previously, and of the genetic alterations which cause them. In so doing, they should provide important insight into the kinds of mechanisms involved in the regulation of cell growth and differentiation.
