REGULATION OF FURROW PROGRESSION IN THE DROSOPHILA EYE BY CAMP-DEPENDENT PROTEIN-KINASE-A

THE earliest physical sign of differentiation in the Drosophila retina is the passage of the morphogenetic furrow across the epithelium of t he eye disc(1,2). Secreted factors encoded by hedgehog (hh)(3-7) and d ecapentaplegic (dpp)(8-10) have been implicated in propagation of the furrow(11,12) and the subsequent initiation of photoreceptor different iation. The morphogenetic furrow initiates at the posterior edge of th e third larval instar eye imaginal disc, Its continued progression tow ards the anterior is believed to depend upon secretion of Hh protein b y the differentiating clusters of photoreceptors that emerge posterior to the moving furrow(11,12). This progression is marked by the initia tion of expression of the transforming growth factor-beta homologue Dp p in cells entering the furrow anteriorly, and loss of dpp expression in cells emerging posteriorly(16,17). Although the transmembrane prote in encoded by the patched gene has been genetically implicated as the Hh receptor(12,18-20), the intercellular signalling pathways involved in these inductive processes remain uncharacterized. Here we show that the catalytic subunit of cyclic AMP-dependent protein kinase A (Pka-C 1)(13-15) is required for the correct spatial regulation of dpp expres sion during eye development. Loss of Pka-C1 function is sufficient to produce an ectopic morphogenetic wave marked by premature ectopic phot oreceptor differentiation and non-autonomous propagation of dpp expres sion. Our results indicate that Pka-C1 lies in a signalling pathway th at controls the orderly temporal progression of differentiation across the eye imaginal disc.