Rogulja Dragana, Rauskolb Cordelia, Irvine Kenneth D
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Dev Cell. 2008 Aug;15(2):309-21. doi: 10.1016/j.devcel.2008.06.003.
Organ growth is influenced by organ patterning, but the molecular mechanisms that link patterning to growth have remained unclear. We show that the Dpp morphogen gradient in the Drosophila wing influences growth by modulating the activity of the Fat signaling pathway. Dpp signaling regulates the expression and localization of Fat pathway components, and Fat signaling through Dachs is required for the effect of the Dpp gradient on cell proliferation. Juxtaposition of cells that express different levels of the Fat pathway regulators four-jointed and dachsous stimulates expression of Fat/Hippo pathway target genes and cell proliferation, consistent with the hypothesis that the graded expression of these genes contributes to wing growth. Moreover, uniform expression of four-jointed and dachsous in the wing inhibits cell proliferation. These observations identify Fat as a signaling pathway that links the morphogen-mediated establishment of gradients of positional values across developing organs to the regulation of organ growth.
器官生长受器官模式形成的影响，但将模式形成与生长联系起来的分子机制仍不清楚。我们发现，果蝇翅膀中的Dpp形态发生素梯度通过调节Fat信号通路的活性来影响生长。Dpp信号传导调节Fat通路成分的表达和定位，并且通过Dachs的Fat信号传导是Dpp梯度对细胞增殖产生影响所必需的。表达不同水平的Fat通路调节因子四关节蛋白（four-jointed）和 Dachsous的细胞并置会刺激Fat/Hippo通路靶基因的表达和细胞增殖，这与这些基因的梯度表达有助于翅膀生长的假设一致。此外，翅膀中四关节蛋白和Dachsous的均匀表达会抑制细胞增殖。这些观察结果表明，Fat是一种信号通路，它将形态发生素介导的跨发育器官的位置值梯度的建立与器官生长的调节联系起来。
