THE DROSOPHILA PIPSQUEAK GENE ENCODES A NUCLEAR BTB-DOMAIN-CONTAININGPROTEIN REQUIRED EARLY IN OOGENESIS

Mutations at the pipsqueak locus affect early patterning in the Drosop hila egg and embryo. We have cloned pipsqueak and found that it is a l arge and complex gene, encoding multiple transcripts and protein isofo rms. One protein, PsqA, is absent in all of the mutants that we have e xamined. We show that PsqA is a nuclear protein present in the germ ce lls and somatically derived follicle cells throughout oogenesis and th at it is required prior to stage one of oogenesis. PsqA contains a BTB (POZ) domain at its amino terminus; additionally, we have identified an evolutionarily conserved motif of unknown function present four tim es in tandem at the C terminus of the protein. PZ pipsqueak mutants pr oduce a putative fusion protein containing the pipsqueak BTB domain fu sed to sequences resident on the PZ element (H. Horowitz and C. Berg, 1995 Genetics 139, 327-335). We demonstrate here that expression of th is fusion protein in wild-type flies has a dominant effect, resulting in infertility and eggshell defects. These dominant phenotypes are dis cussed in light of current theories on the role of the BTB domain in p rotein-protein interactions.