Mechanisms of digit formation: Human malformation syndromes tell the story

Authors

  • Sigmar Stricker,

    Corresponding author
    1. Development and Disease Group, Max Planck-Institute for Molecular Genetics, Berlin, Germany, and Institute for Medical and Human Genetics, Charité University Medicine Berlin, Berlin, Germany
    • Development and Disease Group, Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany
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  • Stefan Mundlos

    Corresponding author
    1. Development and Disease Group, Max Planck-Institute for Molecular Genetics, Berlin, Germany, and Institute for Medical and Human Genetics, Charité University Medicine Berlin, Berlin, Germany
    • Institute for Medical and Human Genetics, Charité University Medicine Berlin, Charité Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany
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Abstract

Identifying the genetic basis of human limb malformation disorders has been instrumental in improving our understanding of limb development. Abnormalities of the hands and/or feet include defects affecting patterning, establishment, elongation, and segmentation of cartilaginous condensations, as well as growth of the individual skeletal elements. While the phenotype of such malformations is highly diverse, the mutations identified to date cluster in genes implicated in a limited number of molecular pathways, namely hedgehog, Wnt, and bone morphogenetic protein. The latter pathway appears to function as a key molecular network regulating different phases of digit and joint development. Studies in animal models not only extended our insight into the pathogenesis of these conditions, but have also contributed to our understanding of the in vivo functions and interactions of these key players. This review is aimed at integrating the current understanding of human digit malformations into the increasing knowledge of the molecular mechanisms of digit development. Developmental Dynamics 240:990–1004, 2011. © 2011 Wiley-Liss, Inc.

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