Disruption of Wnt production in Shh lineage causes bone malformation in mice, mimicking human Malik-Percin-type syndactyly
Disruption of Wnt production in Shh lineage causes bone malformation in mice, mimicking human Malik-Percin-type syndactyly
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Shh 谱系中 Wnt 产生的破坏导致小鼠骨畸形，类似于人类 Malik-Percin 型并指症
DOI：
10.1002/1873-3468.12963
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Zhang Zunyi
中科院分区：
文献类型：
--
作者：
Zhu Xiao Jing;Fang Yukun;Xiong Yanan;Wang Min;Yang Xueqin;Li Yan;Zhang Xiaoyun;Dai Zhong Min;Qiu Mengsheng;Zhang Ze;Zhang Zunyi
在这里，我们表明Shh ‐Cre‐介导的Wnt货物蛋白Wnt tless在小鼠后肢间充质中的缺失导致第3和第4趾的骨并指畸形，类似于人类Malik-Percin类型。Shh后代在野生型肢体中从第5趾到第3趾的后半部分逐渐分布，然而，在WntlessShh ‐Cre中，它们在第3趾的后半部分异常增加。WntlessShh‐ Crimbs显示hedgehog通路基因的表达改变和非经典Wnt信号传导活性受损。我们进一步表明，Wls Shh-Creserved中的前肢间充质细胞作为Wnt 5a的来源，重新定向相邻的Wls-lackingShh谱系细胞向前移动，随后导致并指，这表明异常的间充质细胞运动/凝聚可能是并指发病机制的基础。
Here, we show thatShh‐Cre‐mediated deletion ofWntless, the Wnt cargo protein, in mouse posterior limb mesenchyme causes bone syndactyly of the 3rd and 4th digits, resembling the human Malik–Percin type. TheShhdescendants gradiently distributed from digit 5 to posterior half of digit 3 in wild‐type limbs, however, they abnormally increased in posterior digit 3 inWntlessShh‐Cre.WntlessShh‐Crelimbs displayed altered expression of hedgehog pathway genes and impaired noncanonical Wnt signaling activity. We further showed that the anterior limb mesenchymal cells in theWlsShh‐Creserved as a source of Wnt5a to reorientate the adjacentWls‐lackingShhlineage cells to move anteriorly and subsequently led to syndactyly, suggesting that aberrant mesenchymal cell movement/condensation may underlie the pathogenesis of syndactyly.