Robust, bistable patterning of the dorsal surface of the Drosophila embryo.
Robust, bistable patterning of the dorsal surface of the Drosophila embryo.
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DOI：
10.1073/pnas.0510398103
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发表时间：
2006-08
影响因子：
11.1
通讯作者：
David M. Umulis;M. Serpe;M. O’Connor;H. Othmer
中科院分区：
文献类型：
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作者：
David M. Umulis;M. Serpe;M. O’Connor;H. Othmer
在许多发育系统中，细胞的命运取决于其在形态发生素的时间无关空间分布中的位置。然而，在果蝇胚胎的背腹图案形成过程中，最初的低水平信号细化为窄的高强度带。这种细化表明，细胞响应于局部瞬时形态发生蛋白（BMP），其受体，BMP结合蛋白Sog和Tsg，金属蛋白酶Tld，和一个假定的，正调控的组件，局部增强高信号区域内的BMP表面结合之间的相互作用的结果分布。我们开发了一个计算模型背表面图案，并表明，当正反馈的细胞表面BMP结合蛋白被纳入，双稳态的动力学相互作用转导的瞬时BMP分布成开关样的BMP结合受体的空间分布。我们还表明，包括正反馈导致所观察到的收缩信号，因为背中线附近的细胞胜过相邻的侧细胞的BMP数量有限。在该模型中，细胞通过根据其暴露的历史而不是形态发生素的静态空间梯度中的阈值浓度进行区分来解释形态发生素分布。
In many developing systems, the fate of a cell is determined by its position in a time-independent spatial distribution of a morphogen. However, during dorsal-ventral patterning in the Drosophila embryo, an initial low-level signal refines to a narrow, high-intensity band. This refinement suggests that cells respond to the local transient morphogen distribution that results from interactions between bone morphogenetic proteins (BMPs), their receptors, the BMP-binding proteins Sog and Tsg, the metalloprotease Tld, and a putative, positively regulated component that locally enhances surface binding of BMPs within the region of high signaling. We develop a computational model for dorsal surface patterning and show that, when positive feedback of a cell surface BMP-binding protein is incorporated, bistability in the kinetic interactions transduces the transient BMP distribution into a switch-like spatial distribution of the BMP-bound receptor. We also show that the inclusion of positive feedback leads to the observed contraction of signaling, because cells near the dorsal midline outcompete adjacent lateral cells for limited amounts of BMP. In the model, cells interpret the morphogen distribution by differentiating according to the history of their exposure rather than to a threshold concentration in a static spatial gradient of the morphogen.