Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients
Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients
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DOI：
10.1126/science.1252960
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发表时间：
2014-08-01
期刊：
影响因子：
56.9
通讯作者：
Sharpe, J.
中科院分区：
文献类型：
--
作者：
Raspopovic, J.;Marcon, L.;Sharpe, J.
在肢体发育过程中，足趾从构成肢体芽的未分化间充质组织中出现。有人提出，这一过程是由自组织图灵机制控制的，可扩散的分子相互作用，产生一个周期性的数字和交叉命运模式。然而，分子的身份仍然未知。通过结合实验和建模，我们揭示的证据表明，图灵网络实现的Bmp，Sox9，和Wnt驱动器的数字规格。我们开发了一个现实的二维模拟数字图案，并表明，该网络，当调制的形态梯度，概括的野生型和扰动实验中的Sox 9的表达模式。我们的系统生物学方法揭示了生长，形态梯度和自组织图灵网络的组合如何实现稳健和可重复的模式形成。
During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation.