Disruption of Wnt production in Shh lineage causes bone malformation in mice, mimicking human Malik-Percin-type syndactyly.
Here, we show that Shh-Cre-mediated deletion of Wntless, the Wnt cargo protein, in mouse posterior limb mesenchyme causes bone syndactyly of the 3rd and 4th digits, resembling the human Malik-Percin type. The Shh descendants gradiently distributed from digit 5 to posterior half of digit 3 in wild-type limbs, however, they abnormally increased in posterior digit 3 in WntlessShh-Cre . WntlessShh-Cre limbs displayed altered expression of hedgehog pathway genes and impaired noncanonical Wnt signaling activity. We further showed that the anterior limb mesenchymal cells in the WlsShh-Cre served as a source of Wnt5a to reorientate the adjacent Wls-lacking Shh lineage cells to move anteriorly and subsequently led to syndactyly, suggesting that aberrant mesenchymal cell movement/condensation may underlie the pathogenesis of syndactyly.
['Zhu|Xiao-Jing|XJ|0000-0001-9717-387X', 'Fang|Yukun|Y|', 'Xiong|Yanan|Y|', 'Wang|Min|M|', 'Yang|Xueqin|X|', 'Li|Yan|Y|', 'Zhang|Xiaoyun|X|', 'Dai|Zhong-Min|ZM|', 'Qiu|Mengsheng|M|', 'Zhang|Ze|Z|', 'Zhang|Zunyi|Z|']
D000818:Animals D019521:Body Patterning D019070:Cell Lineage D002478:Cells, Cultured D004195:Disease Models, Animal D005385:Fingers D017353:Gene Deletion D018507:Gene Expression Regulation, Developmental D053823:Hedgehog Proteins D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D059630:Mesenchymal Stem Cells D051379:Mice D043562:Receptors, G-Protein-Coupled D013576:Syndactyly D014034:Toes D060449:Wnt Signaling Pathway
syndactyly hedgehog Wnt signaling genetic animal models limb patterning