A complete developmental and molecular analysis of the 1(2)Cf (Cf) gene in Drosophila melanogaster will be carried out. Cf mutations produce brain hemispheres 5-10x the normal size in late 3rd instar larvae without affecting the ventral ganglion. Cf brain tissue when transplanted into wild type adult hosts becomes tumorous and malignant. The cloned gene is located within 46kb of the dopa decarboxylase gene and is part of the Ddc gene cluster which is involved in catecholamine metabolism and scleroticizaton of the cuticle. Cf mutations also produce a weakened cuticle phenotype in pharate adults and are cell lethals in adult epidermis. Sequencing of the cloned gene will be completed and the derived amino acid sequence examined to determine the nature of the protein and its possible function. Homology to vertebrate genes, some of which may be potential tumor suppressor genes, will be sought. To investigate Cf's role in development, the distribution of its mRNA and protein in tissue sections will be examined. Definitive answers will be sought by studying two aspects of neurogenesis, cell proliferation and differentiation, in mutant and control flies in vivo. The Cf+ gene product may be involved in a specific step in catecholamine metabolism which would implicate a catecholamine derivative not only as a factor in scleroticization of the cuticle but also as a specific neural cell growth regulator in the CNS. To investigate this possibility a survey of biogenic amine pools throughout development and in specific tissue of Cf and wild type will be completed.
