Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients

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Science  01 Aug 2014:
Vol. 345, Issue 6196, pp. 566-570
DOI: 10.1126/science.1252960

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How do fingers know where to grow?

Most researchers today believe that each finger forms because of its unique position within the early limb bud. However, 30 years ago, developmental biologists proposed that the arrangement of fingers followed the Turing pattern, a self-organizing process during early embryo development. Raspopovic et al. provide evidence to support a Turing mechanism (see the Perspective by Zuniga and Zeller). They reveal that Bmp and Wnt signaling pathways, together with the gene Sox9, form a Turing network. The authors used this network to generate a computer model capable of accurately reproducing the patterns that cells follow as the embryo grows fingers.

Science, this issue p. 566; see also p. 516


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.

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