IDENTIFICATION OF HOMEOTIC TARGET GENES IN DROSOPHILA-MELANOGASTER INCLUDING NERVY, A PROTOONCOGENE HOMOLOG

In Drosophila, the specific morphological characteristics of each segm ent are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization proced ure to isolate activated target genes of the homeotic gene Ultrabithor ax (Ubx). In addition, we constructed a set of mutant genotypes that m easures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demons trate that homeotic genes can regulate target gene expression at the s tart of gastrulation, suggesting a previously unknown role for the hom eotic genes at this early stage. We also show that, in abdominal segme nts, the levels of expression for two target genes increase in respons e to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a h uman proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of ta rget gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes.