A Feed-Forward Circuit Linking Wingless, Fat-Dachsous Signaling, and the Warts-Hippo Pathway to Drosophila Wing Growth

被引:111
作者
Zecca, Myriam [1 ,2 ]
Struhl, Gary [1 ,2 ]
机构
[1] Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA
关键词
PLANAR-CELL-POLARITY; TUMOR-SUPPRESSOR PATHWAY; LONG-RANGE ACTION; DORSAL/VENTRAL COMPARTMENT BOUNDARY; GENE-EXPRESSION; MORPHOGEN GRADIENT; ORGAN SIZE; TRANSCRIPTION FACTOR; LIMB DEVELOPMENT; TEAD/TEF FAMILY;
D O I
10.1371/journal.pbio.1000386
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:16
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