Canonical Wnt signaling regulates the proliferative expansion and differentiation of fibrocytes in the murine inner ear
Canonical Wnt signaling regulates the proliferative expansion and differentiation of fibrocytes in the murine inner ear
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DOI：
10.1016/j.ydbio.2014.03.023
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发表时间：
2014-07-01
影响因子：
2.7
通讯作者：
Kispert, Andreas
中科院分区：
文献类型：
--
作者：
Bohnenpoll, Tobias;Trowe, Mark-Oliver;Kispert, Andreas
耳纤维细胞将耳蜗导管与周围的耳囊相连，但也至关重要地参与维持耳蜗中的离子稳态，从而影响声音的感知。调节这种来自间充质前体的异质细胞群发育的分子途径知之甚少。在这里，我们确定上皮 Wnt7a 和 Wnt7b 是邻近未分化周膜间充质 (POM) 中 Fzd 介导的 β-连环蛋白 (Ctnnb1) 依赖性（规范）Wnt 信号传导的可能配体。 POM中有条件删除Ctnnb1的小鼠表现出纤维细胞分化完全失败、耳蜗管周围间充质细胞严重减少、耳蜗周围空间丧失、骨囊增厚和部分丧失以及出生前不久耳蜗管卷曲的继发性紊乱。早期阶段的分析表明，在具有高度浓缩的软骨前体和排列更松散的内部间充质细胞的两个区域中，POM 的径向图案正常发生，但内部区域的增殖减少且细胞分化失败。在整个 POM 间充质中错误/过度表达 Ctnnb1 稳定形式的细胞分选至内部间充质室，并表现出增殖增加。我们的分析表明，来自耳蜗管上皮的 Wnt 信号对于诱导纤维细胞前体细胞的分化和扩增至关重要。我们的研究结果强调了上皮间质信号传导在内耳发育中的重要性。 (C) 2014 Elsevier Inc. 保留所有权利。
Otic fibrocytes tether the cochlear duct to the surrounding otic capsule but are also critically involved in maintenance of ion homeostasis in the cochlea, thus, perception of sound. The molecular pathways that regulate the development of this heterogenous group of cells from mesenchymal precursors are poorly understood. Here, we identified epithelial Wnt7a and Wnt7b as possible ligands of Fzd-mediated beta-catenin (Ctnnb1)-dependent (canonical) Wnt signaling in the adjacent undifferentiated periotic mesenchyme (POM). Mice with a conditional deletion of Ctnnb1 in the POM exhibited a complete failure of fibrocyte differentiation, a severe reduction of mesenchymal cells surrounding the cochlear duct, loss of pericochlear spaces, a thickening and partial loss of the bony capsule and a secondary disturbance of cochlear duct coiling shortly before birth. Analysis at earlier stages revealed that radial patterning of the POM in two domains with highly condensed cartilaginous precursors and more loosely arranged inner mesenchymal cells occurred normally but that proliferation in the inner domain was reduced and cytodifferentiation failed. Cells with mis/overexpression of a stabilized form of Ctnnb1 in the entire POM mesenchyme sorted to the inner mesenchymal compartment and exhibited increased proliferation. Our analysis suggests that Wnt signals from the cochlear duct epithelium are crucial to induce differentiation and expansion of fibrocyte precursor cells. Our findings emphasize the importance of epithelial-mesenchymal signaling in inner ear development. (C) 2014 Elsevier Inc. All rights reserved.