Antagonistic Growth Regulation by Dpp and Fat Drives Uniform Cell Proliferation

Antagonistic Growth Regulation by Dpp and Fat Drives Uniform Cell Proliferation
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DOI:
10.1016/j.devcel.2010.11.007
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发表时间:
2011-01-18
期刊:
影响因子:
11.8
通讯作者:
Basler, Konrad
Basler, Konrad
中科院分区:
生物学1区
文献类型:
--
作者:
Schwank, Gerald;Tauriello, Gerardo;Basler, Konrad

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我们使用果蝇翼盘中的DPP形态原梯度作为模型来解决生长因子的梯度如何产生均匀生长的根本问题。我们首先证明了脂肪肿瘤抑制通路中各成分的适当表达和亚细胞定位,已经被证明依赖于DPP活性差异,而不是依赖于DPP梯度。接下来,我们分析了具有一致高DPP或一致低脂肪信号活性的椎间盘中的细胞增殖,发现这些途径以互补的方式调节生长。DPP介体Brinker主要在外侧区域抑制原基的生长,而FAT主要抑制内侧区域的生长。综上所述,我们的结果表明,这两个信号通路的活性是以平行的方式而不是顺序的方式调节的,并且通过它们对生长的互补作用来实现均匀的增殖。
We use the Dpp morphogen gradient in the Drosophila wing disc as a model to address the fundamental question of how a gradient of a growth factor can produce uniform growth. We first show that proper expression and subcellular localization of components in the Fat tumor-suppressor pathway, which have been argued to depend on Dpp activity differences, are not reliant on the Dpp gradient. We next analyzed cell proliferation in discs with uniformly high Dpp or uniformly low Fat signaling activity and found that these pathways regulate growth in a complementary manner. While the Dpp mediator Brinker inhibits growth in the primordium primarily in the lateral regions, Fat represses growth mostly in the medial region. Together, our results indicate that the activities of both signaling pathways are regulated in a parallel rather than sequential manner and that uniform proliferation is achieved by their complementary action on growth.