Requirement for Drosophila 14-3-3ζ in Raf-dependent photoreceptor development

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