The tumorous head phenotype (masses of abdominal and genital tissue arising where the eye ought to be) in Drosophila melanogaster is produced by the interaction of the maternally acting tuh-1 locus with the zygotically acting Tuh-3 mutation in the following fashion. In progeny of tuh-1+ femalesTuh-3 produces no observable phenotype. Progeny of tuh-1- females are normal in phenotype unless they are also homo- or heterozygous for Tuh-3. Tuh-3 progeny of tuh-1- (loss of function) mutant females have the tumorous head phenotype. Tuh-3/Tuh-3 (but not Tuh-3/+) progeny of females carrying the dominant naturally occurring tuh-1g allele have normal heads, but have defects in the development of derivatives of the genital disc. The effect of the Tuh-3 thus depends on the maternal genotype at the tuh-1 locus. TheTuh-3 mutation is apparently caused by an insertion of a Delta-88 element into one of the most distal sites in the Bithorax Complex (BX-C), and presumably causes its effects by disrupting the regulation of the expression of this part of the BX-C. The work proposed here is to elucidate the molecular mechanism of the unusual interaction between tuh-1 andTuh-3 by addressing two issues. First tuh-1 will be cloned and the clones will be used to obtain information about the nature of the product encoded by this gene, about its developmental time and place of appearance, and the differences among products encoded by wild type, loss of function, and g alleles. Second, reversion and DNA lesion mapping studies are planned to determine whether the interaction takes place via the Delta-88 element in the BX-C, or via regulatory sites near the site of this insertion. This is a study of a very unusual interaction between two genes, in which the developmental defect caused by a particular mutation at one gene in a fly is very different depending on which form of a second gene was present in the mother of that fly. The first gene is a member of the Bithorax Complex, a set of genes which determines the segmental identities of the thoracic and abdominal segments. In order to ensure proper identities for each segment, the genes in this complex are regulated in a very precise and complex pattern, the details of which are still being worked out. The mechanism of this regulation is still obscure, although it is clear that interaction with other genes outside the complex is involved. Interactions among developmentally important genes are an important, and as yet poorly understood, component of the mechanism by which such genes bring about the development of the pattern of an organism. This study should shed light on how such interactions take place.
