REQUIREMENT FOR DROSOPHILA 13-3-3-ZETA IN RAF-DEPENDENT PHOTORECEPTORDEVELOPMENT

Based on biochemical and functional data obtained with tissue culture cells and yeast, 14-3-3 proteins have been implicated in a number of d ifferent signal transduction processes, in particular in the signal-de pendent activation of protein kinases. We performed a functional analy sis of 14-3-3 in a multicellular organism, initiated by the cloning of a 14-3-3 zeta homolog of Drosophila melanogaster, termed D14-3-3 zeta . D14-3-3 zeta transcripts are strongly enriched in the developing cen tral nervous system. In addition, they are predominantly expressed in the region posterior to the morphogenetic furrow of the eye imaginal d isc where cells differentiate as photoreceptors. In these cells D14-3- 3 zeta is localized apically. Both the expression pattern and the subc ellular localization are consistent with the proposed function of 14-3 -3 proteins in Ras/Raf/MAPK signaling. D14-3-3 zeta mutant analysis co mbined with rescue experiments involving gain-of-function alleles of R af and Ras indicate that D14-3-3 zeta is an essential component of the Raf/Ras signaling pathway and necessary for photoreceptor differentia tion. It acts upstream of Raf and downstream of Ras.