OVO transcription factors function antagonistically in the Drosophila female germline. J. Andrews ¹, D. Garcia-Estefania ², I. Delon ³, J. Lü ¹, M. Mével-Ninio ⁴, A. Spierer ², F. Payre ³, D. Pauli ², B. Oliver ¹. 1) Lab Cell & Dev Biol, NIDDK, National Institutes of Health, Bethesda, MD; 2) Department of Zoology and Animal Biology, University of Geneva, Geneva CH; 3) Centre de Biologie du Développement, UMR 5547, Toulouse FR; 4) Centre de Génétique Moléculaire du CNRS, Gif-sur-Yvette FR.

   OVO controls germline and epidermis differentiation in flies and mice. In the Drosophila germline, alternative OVO-B and OVO-A isoforms have a common DNA-binding domain, but different N-termini. Using multiple assays we show that these isoforms are transcription factors with opposite regulatory activities. In yeast one-hybrid assays, we identified a strong activation domain within a common region and a counteracting repression domain within the OVO-A-specific region. In flies, OVO-B positively regulated the ovarian tumorpromoter, while OVO-A was a negative regulator of the ovarian tumorand ovopromoters. OVO-B isoforms supplied wildtype ovofunction in the female germline and epidermis, while OVO-A isoforms had dominant-negative activity in both tissues. Moreover, elevated expression of OVO-A resulted in maternal-effect lethality, while the absence of OVO-A resulted in maternal-effect sterility. Our data indicate that tight regulation of antagonistic OVO-B and OVO-A isoforms is critical for germline formation and differentiation.