Molecular analysis of the neurogenic locus mastermind of Drosophila melanogaster.

The neurogenic loci comprise a small group of genes which are required for proper division between the neural and epidermal pathways of differentiation within the neuroectoderm. Loss of neurogenic gene function results in the misrouting of prospective epidermal cells into neuroblasts. A molecular analysis of the neurogenic locus mastermind (mam) has been initiated through transposon tagging with P elements. Employing the Harwich strain as the source of P in a hybrid dysgenesis screen, 6000 chromosomes were tested for the production of lethal mam alleles and eight mutations were isolated. The mam region is the site of residence of a P element in Harwich which forms the focus of a chromosome breakage hotspot. Hybrid dysgenic induced mam alleles elicit cuticular and neural abnormalities typical of the neurogenic phenotype, and in five of the eight cases the mutants appear to retain a P element in the cytogenetic region (50CD) of mam. Utilizing P element sequence as probe, mam region genomic DNA was cloned and used to initiate a chromosome walk extending over 120 kb. The physical breakpoints associated with the hybrid dysgenic alleles fall within a 60-kb genomic segment, predicting this as the minimal size of the mam locus barring position effects. The locus contains a high density of repeated elements of two classes; opa (CAX)n and (dC-dA)n.(dG-dT)n. A preliminary study of the transcriptional activity of the mam region is presented.