SoxF is part of a novel negative-feedback loop in the wingless pathway that controls proliferation in the Drosophila wing disc

9 páginas, 6 figuras. Supplementary material for this article is available at http://dev.biologists.org/cgi/content/full/136/5/761/DC1Wnt molecules act as mitogenic signals during the development of multiple organs, and the aberrant activity of their pathway is often associated with cancer. Therefore, the production of Wnts and the activity of their signaling pathway must be tightly regulated. We have investigated the mechanisms of this regulation in the Drosophila hinge, a domain within the wing imaginal disc that depends on the fly Wnt1 ortholog wingless (wg) for its proliferation. Our results uncover a new feedback loop in the wg pathway in which the spatially restricted activation of the Sox gene SoxF (Sox15) by wg represses its own transcription, thus ensuring tight regulation of growth control. rotund, a wing proximodistal patterning gene, excludes SoxF from a thin rim of cells. These cells are thus allowed to express wg and act as the source of mitogenic signal. This novel mode of action of a Sox gene on the Wnt pathway - through transcriptional repression of a Wnt gene - might be relevant to human disease, as loss of human SoxF genes has been implicated in colon carcinoma.This work was funded through grants BMC2003-06248 and BFU2006-00349 to F.C. and the Consolider consortium `From Genes to Shape', of which F.C. is a participant researcher, all from the Spanish Ministry of Science and Innovation. M.L.-D.D. was funded by the FRM (Fondation pour la Recherche Medicale), the Juan de la Cierva Program (Spanish Ministry of Science and Education) and a Marie-Curie Intra-European Postdoctoral contract (EIF). J.C. is a predoctoral fellow of the Portuguese Fundação para a Ciência e a Tecnologia.Peer reviewe