The PHD zinc finger protein Rhinoceros is a negative regulator of Ras signalling in the developing eye. M.G. Voas , I. Rebay. Whitehead Inst Biomedical Res, MIT, Cambridge, MA.

   In the Drosophila eye, the DER/Ras/MAPK signalling pathway is required to sequentially recruit photoreceptors, cone and pigment cells into the developing ommatidium. Loss of function in genes which negatively regulate this pathway, such as argos, results in the overproduction of numerous cell types. Here we present genetic and biochemical data which describe a new antagonist of DER/Ras/MAPK signalling, rhinoceros. Loss of rhinocerosfunction in the eye results in extra outer photoreceptors, while loss of function in the antenna results in an arista to leg transformation. Conversely, transgenic overexpression of rhinocerosin the eye results in the reduction in the number of cells. Alleles of rhinoceros show a strong, dominant enhancement effect on the eye phenotype of argosmutants. Likewise, rhinoceros alleles can suppress an eye phenotype caused by overexpression of argos, and rhinoceros, argosdouble mutant eyes have a much stronger phenotype than either mutant alone. The ability of rhinoceros to modify the eye phenotype of pointed, which encodes an ETS domain transcription factor, further supports its role as a regulator of DER/Ras/MAPK signalling. Rhinoceros is a PHD class zinc finger protein with several human homologs. Rhinoceros protein is widely expressed during Drosophila embryonic development, and its localization to the nucleus suggests a role in transcriptional regulation. We have used S2 cell based assays to show that Rhinoceros inhibits transcription of genes downstream of DER/Ras/MAPK. Specifically, we find that the ability of Pointed P2 and RasV12 to drive expression from an ETS binding site-Luciferase construct is inhibited in the presence of Rhinoceros. Together, these data provide both genetic and biochemical functions for a new negative regulator of DER/Ras/MAPK signalling. Further studies will investigate potential binding partners and clarify how Rhinoceros is used to limit pathway activity in the context of the developing eye.