The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through Notch activation

Recent studies in vertebrates and Drosophila melanogaster have revealed tha t Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis(1,2). In these processes, a homeobox-conta ining transcription factor is responsible for spatially regulating fringe ( fng) expression and thus directing activation of the Notch pathway along th e fng expression border. Here we show that this may be a general mechanism for patterning epithelial cell layers. At three stages in Drosophila oogene sis, mirror (mirr) and fng have complementary expression patterns in the fo llicle-cell epithelial layer, and at all three stages loss of mirr enlarges , and ectopic expression of mirr restricts, fng expression, with consequenc es for follicle-cell patterning. These morphological changes are similar to those caused by Notch mutations. Ectopic expression of mirr in the posteri or follicle cells induces a stripe of rhomboid (rho) expression and repress es pipe (pip), a gene with a role in the establishment of the dorsal-ventra l axis, at a distance. Ectopic Notch activation has a similar long-range ef fect on pip. Our results suggest that Mirror and Notch induce secretion of diffusible morphogens and we have identified TGF-beta (encoded by dpp) as s uch a molecule in germarium. We also found that mirr expression in dorsal f ollicle cells is induced by the EGF-receptor (EGFR) pathway and that mirr t hen represses pip expression in all but the ventral follicle cells, connect ing EGFR activation in the dorsal follicle cells to repression of pip in th e dorsal and lateral follicle cells. Our results suggest that the different iation of ventral follicle cells is not a direct consequence of germline si gnalling, but depends on long-range signals from dorsal follicle cells, and provide a link between early and late events in Drosophila embryonic dorsa l-ventral axis formation.