Free extracellular diffusion creates the Dpp morphogen gradient of the Drosophila wing disc.

Free extracellular diffusion creates the Dpp morphogen gradient of the Drosophila wing disc.
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DOI:
10.1016/j.cub.2012.02.065
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发表时间:
2012-04-24
期刊:
影响因子:
9.2
通讯作者:
Lander, Arthur D.
Lander, Arthur D.
中科院分区:
生物学1区
文献类型:
--
作者:
Zhou, Shaohua;Lo, Wing-Cheong;Suhalim, Jeffrey L.;Digman, Michelle A.;Gratton, Enrico;Nie, Qing;Lander, Arthur D.

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形态梯度是如何形成的一直是一个有争议的话题。形态形成因子不是简单地通过自由扩散来传播的观点,最有力的支持来自于对果蝇幼虫翅盘的十足麻痹(Dpp)梯度的各种研究。在本研究中,我们首先展示了在这些研究中,考虑转运与受体介导的摄取和降解耦合的失败是如何导致转运率的估计低了几个数量级,从而为各种假设机制提供了毫无根据的支持,例如“平面胞吞”和“限制性细胞外扩散”。使用几种独立的动态方法,我们获得的数据与这些模型不一致,并且直接表明Dpp转运是通过细胞外空间的简单,快速扩散发生的。我们讨论了这些发现对其他形态形成系统的影响,其中复杂的运输机制已被提出。我们相信这些发现解决了一个主要的、长期存在的关于形态梯度形成的问题,并为解释形态梯度动力学的实验观察提供了一个坚实的框架。
How morphogen gradients form has long been a subject of controversy. The strongest support for the view that morphogens do not simply spread by free diffusion has come from a variety of studies of the Decapentaplegic (Dpp) gradient of the Drosophila larval wing disc. In the present study, we initially show how the failure, in such studies, to consider the coupling of transport to receptor-mediated uptake and degradation has led to estimates of transport rates that are orders of magnitude too low, lending unwarranted support to a variety of hypothetical mechanisms, such as “planar transcytosis” and “restricted extracellular diffusion”. Using several independent dynamic methods, we obtain data that are inconsistent with such models, and that show directly that Dpp transport occurs by simple, rapid diffusion in the extracellular space. We discuss the implications of these findings for other morphogen systems in which complex transport mechanisms have been proposed. We believe that these findings resolve a major, longstanding question about morphogen gradient formation, and provide a solid framework for interpreting experimental observations of morphogen gradient dynamics.
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