REVERSE GENETICS OF DROSOPHILA BRAIN STRUCTURE AND FUNCTION

A set of molecular genetic technologies are described, which will have far reaching consequences for the study of brain structure, function and development in Drosophila melanogaster. Site selected mutagenesis (a PCR-based screen for P-element insertion events) allows insertion m utants to be isolated for any cloned gene, and is being used in this l aboratory to ask questions about the rolls of particular cellular comp onents in learning and memory. Transposants have been isolated in gene s encoding a regulatory (RI) and a catalytic (DCO) subunit of cAMP-dep endent protein kinase, and in a gene encoding a Gi-like alpha subunit. The alternative use of I factors is described. The PKA RI homozygous mutants display a significant decrement in initial learning ability. E nhancer-trap strategies, for which the GAL-4 P-element system is parti cularly convenient, allow the identification of genes expressed in the developing fly brain. Strategies for the efficient detection of such events are described.