a feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to drosophila wing growth前馈电路连接无翅、fat-dachsous信号和果蝇翅膀增长warts-hippo通路.pdfVIP

A Feed-Forward Circuit Linking Wingless, Fat-Dachsous Signaling, and the Warts-Hippo Pathway to Drosophila Wing Growth Myriam Zecca1,2, Gary Struhl1,2* 1 Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York, United States of America, 2 Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York, United States of America Abstract During development, the Drosophila wing primordium undergoes a dramatic increase in cell number and mass under the control of the long-range morphogens Wingless (Wg, a Wnt) and Decapentaplegic (Dpp, a BMP). This process depends in part on the capacity of wing cells to recruit neighboring, non-wing cells into the wing primordium. Wing cells are defined by activity of the selector gene vestigial (vg) and recruitment entails the production of a vg-dependent ‘‘feed-forward signal’’ that acts together with morphogen to induce vg expression in neighboring non-wing cells. Here, we identify the protocadherins Fat (Ft) and Dachsous (Ds), the Warts-Hippo tumor suppressor pathway, and the transcriptional co-activator Yorkie (Yki, a YES associated protein, or YAP) as components of the feed-forward signaling mechanism, and we show how this mechanism promotes wing growth in response to Wg. We find that vg generates the feed-forward signal by creating a steep differential in Ft-Ds signaling between wing and non-wing cells. This differential down-regulates Warts-Hippo pathway activity in non-wing cells, leading to a burst of Yki activity and the induction of vg in response to Wg. We posit that Wg propels wing growth at least in part by fueling a wave front of Ft-Ds signaling that propagates vg expression from one cell to the next. Citation: Zecca M, Struhl G (2010) A Feed-Forward