Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning
Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning
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DOI：
10.1038/nature03318
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发表时间：
2005-03-10
期刊：
影响因子：
64.8
通讯作者：
Ferguson, EL
中科院分区：
文献类型：
--
作者：
Wang, YC;Ferguson, EL
在许多发育背景下，局部产生的形态原通过在细胞场上形成浓度梯度来指定位置信息（1）。然而，在果蝇的胚胎背腹模式形成期间，骨形态发生蛋白（BMP）家族的两个成员十肢麻痹（Dpp）和螺旋（Scw）被广泛转录，但在表达细胞的有限亚群中促进受体介导的信号传导（2-4）。在这里，我们使用一种新的免疫染色方案，以可视化受体结合骨形态发生蛋白，并显示这两种蛋白质成为本地化的背细胞的一个尖锐的条纹。我们证明，适当的BMP本地化涉及两个不同的过程。首先，Dpp经历定向的、长距离的细胞外转运。Scw也进行远程移动，但可以独立于Dpp运输。第二，细胞内正反馈电路促进未来的配体结合作为以前的信号强度的函数。这些数据引出了一个模型，其中细胞外Dpp转运最初产生BMP结合的浅梯度，其通过细胞内正反馈作用以产生BMP -受体相互作用的两种稳定状态，空间双稳态，其中BMP结合和信号传导能力在背侧细胞中高，在侧细胞中低。
In many developmental contexts, a locally produced morphogen specifies positional information by forming a concentration gradient over a field of cells(1). However, during embryonic dorsal - ventral patterning in Drosophila, two members of the bone morphogenetic protein (BMP) family, Decapentaplegic (Dpp) and Screw (Scw), are broadly transcribed but promote receptor-mediated signalling in a restricted subset of expressing cells(2-4). Here we use a novel immunostaining protocol to visualize receptor-bound BMPs and show that both proteins become localized to a sharp stripe of dorsal cells. We demonstrate that proper BMP localization involves two distinct processes. First, Dpp undergoes directed, long-range extracellular transport. Scw also undergoes long-range movement, but can do so independently of Dpp transport. Second, an intracellular positive feedback circuit promotes future ligand binding as a function of previous signalling strength. These data elicit a model in which extracellular Dpp transport initially creates a shallow gradient of BMP binding that is acted on by positive intracellular feedback to produce two stable states of BMP - receptor interactions, a spatial bistability in which BMP binding and signalling capabilities are high in dorsal-most cells and low in lateral cells.