The balance of WNT and FGF signaling influences mesenchymal stem cell fate during skeletal development.
The balance of WNT and FGF signaling influences mesenchymal stem cell fate during skeletal development.
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DOI：
10.1126/scisignal.2000727
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发表时间：
2010-05-25
影响因子：
7.3
通讯作者：
Hsu W
中科院分区：
文献类型：
--
作者：
Maruyama T;Mirando AJ;Deng CX;Hsu W
颅缝早闭是一种由于颅骨之间的间隙（骨缝）过早闭合而导致的发育障碍，可由膜内骨化过度引起，膜内骨化是一种不涉及软骨模板形成（软骨发生）的骨形成方式。在此，我们表明软骨内骨化（一种通过软骨中间体进行的骨形成方式，由间充质干细胞向软骨细胞的命运转变引起）也可导致颅缝早闭。在小鼠中同时敲除Axin2（WNT - β - 连环蛋白通路的负调节因子）以及降低成纤维细胞生长因子（FGF）受体1（FGFR1）的活性会诱导异位软骨发生，导致骨缝形态发生异常和融合。遗传分析显示，β - 连环蛋白的激活与FGFR1协同改变间充质干细胞分化为软骨细胞（软骨由此形成）的谱系定向。我们发现WNT - β - 连环蛋白通路通过调节干细胞的更新和增殖直接控制干细胞群体，并通过设定FGF和骨形态发生蛋白通路的平衡间接调节谱系特化。这项研究确定软骨内骨化是发育过程中骨缝闭合的一种机制，并表明该过程与颅缝早闭有关。
Craniosynostosis, a developmental disorder resulting from premature closure of the gaps (sutures) between skull bones, can be caused by excessive intramembranous ossification, a type of bone formation that does not involve formation of a cartilage template (chondrogenesis). Here, we show that endochondral ossification, a type of bone formation that proceeds through a cartilage intermediate, caused by switching the fate of mesenchymal stem cells to chondrocytes, can also result in craniosynostosis. Simultaneous knockout of Axin2, a negative regulator of the WNT–β-catenin pathway, and decreased activity of fibroblast growth factor (FGF) receptor 1 (FGFR1) in mice induced ectopic chondrogenesis, leading to abnormal suture morphogenesis and fusion. Genetic analyses revealed that activation of β-catenin cooperated with FGFR1 to alter the lineage commitment of mesenchymal stem cells to differentiate into chondrocytes, from which cartilage is formed. We showed that the WNT–β-catenin pathway directly controlled the stem cell population by regulating its renewal and proliferation, and indirectly modulated lineage specification by setting the balance of the FGF and bone morphogenetic protein pathways. This study identifies endochondral ossification as a mechanism of suture closure during development and implicates this process in craniosynostosis.
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普法伊弗综合征成纤维细胞生长因子受体1基因的常见突变
影响因子：
30.8
作者：
MUENKE, M;SCHELL, U;WINTER, RM
通讯作者：
WINTER, RM
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.1
作者：
KREIBORG, S;MARSH, JL;VANNIER, MW
通讯作者：
VANNIER, MW
影响因子：
11.8
作者：
Day, TF;Guo, XZ;Yang, YZ
通讯作者：
Yang, YZ
影响因子：
6.2
作者：
Billings, Paul C.;Fiori, Jennifer L.;Kaplan, Frederick S.
通讯作者：
Kaplan, Frederick S.