Three broad areas of research are proposed which ultimately aim at explaining the underlying genetic and molecular mechanisms which are responsible for the specification, differentiation and assembly of the visual system in the fruitfly Drosophila melanogaster. In the first project, experiments are put forward which have as their goal the genetic and molecular characterization of the l(1)ogre locus and ultimately its gene product; mutations at this locus are associated with pronounced deficits in the normal structure of the developing and mature optic lobes and of other subsets of the central nervous system which are believed to be imaginal-specific. In the second project, the ultimate goal is to probe the role of cell-surface glycoproteins in the myriad of interactions which are believed to be necessary for the proper assembly and maintenance of structure in nervous system. To this end, the nature of the synthesis of N-linked glycoproteins in the fly is being investigated and mutants resistant to drugs which specifically target this pathway are being sought. Such mutants will be characterized genetically and biochemically, and the effects of abberations in normal glycoprotein metabolism on the development of the visual system in the wild-type and relevant mutants examined. In the third project, novel mutants are sought on the basis of a particular hypothesis which has never before been systematically pursued in the study of the fly's visual system. Previously, one of the chief advantages of the fly's visual system was perceived as being its dispensability for the viability of the fly. The inherent assumption in much of the genetic analysis was the belief that one would be able to uncover the subset of the genome whose function was unique to the visual system. In the current application, it is proposed that this is a relatively small subset which is operable primarily at the terminus of development and that the subset/s of the genome of primary function in the development of the visual system function prominently in the development fo vital systems in the fly as well. A screen based on the examination of function of knowm organismal lethals as somatic recombinant clones in the eye is proposed.
