Control of Dpp morphogen signalling by a secreted feedback regulator
Control of Dpp morphogen signalling by a secreted feedback regulator
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DOI：
10.1038/ncb2064
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发表时间：
2010-06-01
影响因子：
21.3
通讯作者：
Pyrowolakis, George
中科院分区：
文献类型：
--
作者：
Vuilleumier, Robin;Springhorn, Alexander;Pyrowolakis, George
在许多情况下，在发育过程中，形态发生素通过形成浓度梯度来指定细胞的命运。在黑腹果蝇翅的成虫盘中，十肢麻痹蛋白（Dpp）是一种骨形态发生蛋白（BMP），其功能是作为远程形态发生素来控制图案形成和生长（1）。Dpp从前-后室边界处的一条细胞分泌，并扩散到两个室中以产生特征性BMP活性梯度（2-6）。自从在发育中的翅膀中鉴定出Dpp的形态发生活性以来，该系统一直是了解长程梯度如何建立以及细胞如何对这种梯度做出反应的范例。在这里，我们揭示了这两个过程的紧密和直接的连接与鉴定和表征的五角体（pentagone），BMP信号的转录靶编码的分泌调节的途径。在翅盘中缺乏BMP导致BMP活性梯度的严重收缩，从而导致图案化和生长缺陷。我们表明，Pent与磷脂酰肌醇蛋白聚糖Dally相互作用，以控制Dpp分布，并提供证据表明，正确建立BMP形态梯度需要内置的反馈回路体现Pent。
In many instances during development, morphogens specify cell fates by forming concentration gradients. In the Drosophila melanogaster wing imaginal disc, Decapentaplegic (Dpp), a bone morphogenetic protein (BMP), functions as a long-range morphogen to control patterning and growth(1). Dpp is secreted from a stripe of cells at the anterior-posterior compartment boundary and spreads into both compartments to generate a characteristic BMP activity gradient(2-6). Ever since the identification of the morphogen activity of Dpp in the developing wing, the system has served as a paradigm to understand how long-range gradients are established and how cells respond to such gradients. Here we reveal the tight and direct connection of these two processes with the identification and characterization of pentagone (pent), a transcriptional target of BMP signalling encoding a secreted regulator of the pathway. Absence of pent in the wing disc causes a severe contraction of the BMP activity gradient resulting in patterning and growth defects. We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent.