Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.
Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.
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在成骨细胞和真皮祖细胞的规范和分化中，对颅外胚层和间质衍生的WNT的不同要求。
DOI：
10.1371/journal.pgen.1004152
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发表时间：
2014-02
期刊：
影响因子：
4.5
通讯作者：
Atit RP
中科院分区：
文献类型：
--
作者：
Goodnough LH;Dinuoscio GJ;Ferguson JW;Williams T;Lang RA;Atit RP
颅骨和真皮由外胚层表面下的间充质分化而来。颅间充质中的命运选择需要典型的Wnt效应分子β-连环蛋白，但Wnt配体来源在该过程中的相对贡献仍然未知。在这里，我们表明Wnt配体表达在颅表面外胚层和下面的眶上间充质在真皮和成骨细胞的命运选择。使用条件遗传学，我们消除了所有Wnt配体从颅表面外胚层或未分化的间充质的分泌，以揭示外胚层和间充质来源的Wnt的不同作用。外胚层Wnt配体诱导成骨细胞和真皮成纤维细胞祖细胞特化，同时启动间充质Wnt亚群的表达。间质Wnt配体随后在真皮和成骨细胞祖细胞的分化过程中是必不可少的。最后，外胚层衍生的Wnt配体提供了一个诱导线索，颅间充质的真皮成纤维细胞和成骨细胞谱系的命运选择。因此，Wnt配体的两个来源在成骨细胞和真皮成纤维细胞形成期间执行不同的功能。颅面畸形是相对常见的先天性出生缺陷，Wnt信号通路及其效应子在颅面发育中起关键作用。Wntless/Gpr 177是有效分泌所有Wnt配体所必需的，并映射到含有与骨量减少强烈相关的SNP的区域，杂合缺失与面部畸形相关。在这里，我们测试的作用，分泌的Wnt蛋白的特定来源在颅面发育的早期阶段，并获得了戏剧性的颅面异常。我们发现，上覆的颅表面外胚层Wnt产生的Wnt信号传导的颅骨和皮肤细胞的命运选择和转录的额外的Wnt在下面的间充质的指导线索。一旦启动，间充质Wnt可以维持Wnt信号转导，并在颅骨和皮肤分化过程中以自分泌方式发挥作用。这些结果突出了来自两个特定组织来源的Wnt配体如何整合用于正常颅面图案化，并且可以导致复杂的颅面异常。
The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation. Craniofacial abnormalities are relatively common congenital birth defects, and the Wnt signaling pathway and its effectors have key roles in craniofacial development. Wntless/Gpr177 is required for the efficient secretion of all Wnt ligands and maps to a region that contains SNPs strongly associated with reduced bone mass, and heterozygous deletion is associated with facial dysmorphology. Here we test the role of specific sources of secreted Wnt proteins during early stages of craniofacial development and obtained dramatic craniofacial anomalies. We found that the overlying cranial surface ectoderm Wnts generate an instructive cue of Wnt signaling for skull bone and skin cell fate selection and transcription of additional Wnts in the underlying mesenchyme. Once initiated, mesenchymal Wnts may maintain Wnt signal transduction and function in an autocrine manner during differentiation of skull bones and skin. These results highlight how Wnt ligands from two specific tissue sources are integrated for normal craniofacial patterning and can contribute to complex craniofacial abnormalities.
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
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10.1073/pnas.1006437108
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