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Mechanisms of digit formation: Human malformation syndromes tell the story
Author(s) -
Stricker Sigmar,
Mundlos Stefan
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22565
Subject(s) - biology , numerical digit , limb development , wnt signaling pathway , phenotype , hedgehog , mechanism (biology) , function (biology) , sonic hedgehog , genetics , loss function , bone morphogenetic protein , neuroscience , anatomy , gene , evolutionary biology , bioinformatics , philosophy , arithmetic , mathematics , epistemology
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.