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基于tectonin的基质和平面细胞极性基因是发育中的盖膜中正常胶原纤维定向所必需的。

A tectorin-based matrix and planar cell polarity genes are required for normal collagen-fibril orientation in the developing tectorial membrane.

作者信息

Goodyear Richard J, Lu Xiaowei, Deans Michael R, Richardson Guy P

机构信息

Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK

Department of Cell Biology, University of Virginia Health System, Charlottesville, VA 22098, USA.

出版信息

Development. 2017 Nov 1;144(21):3978-3989. doi: 10.1242/dev.151696. Epub 2017 Sep 21.

Abstract

The tectorial membrane is an extracellular structure of the cochlea. It develops on the surface of the auditory epithelium and contains collagen fibrils embedded in a tectorin-based matrix. The collagen fibrils are oriented radially with an apically directed slant - a feature considered crucial for hearing. To determine how this pattern is generated, collagen-fibril formation was examined in mice lacking a tectorin-based matrix, epithelial cilia or the planar cell polarity genes and In wild-type mice, collagen-fibril bundles appear within a tectorin-based matrix at E15.5 and, as fibril number rapidly increases, become co-aligned and correctly oriented. Epithelial width measurements and data from mice suggest, respectively, that radial stretch and cilia play little, if any, role in determining normal collagen-fibril orientation; however, evidence from tectorin-knockout mice indicates that confinement is important. PRICKLE2 distribution reveals the planar cell polarity axis in the underlying epithelium is organised along the length of the cochlea and, in mice in which this polarity is disrupted, the apically directed collagen offset is no longer observed. These results highlight the importance of the tectorin-based matrix and epithelial signals for precise collagen organisation in the tectorial membrane.

摘要

盖膜是耳蜗的一种细胞外结构。它在听觉上皮表面发育,含有嵌入基于tectin的基质中的胶原纤维。胶原纤维呈放射状排列,顶端有倾斜——这一特征被认为对听力至关重要。为了确定这种模式是如何产生的,在缺乏基于tectin的基质、上皮纤毛或平面细胞极性基因的小鼠中检查了胶原纤维的形成。在野生型小鼠中,胶原纤维束在E15.5时出现在基于tectin的基质内,并且随着纤维数量迅速增加,变得共排列且方向正确。上皮宽度测量和来自小鼠的数据分别表明,径向拉伸和纤毛在确定正常胶原纤维方向方面作用很小(如果有作用的话);然而,来自tectin基因敲除小鼠的证据表明限制很重要。PRICKLE2分布揭示了下层上皮中的平面细胞极性轴沿耳蜗长度方向排列,并且在这种极性被破坏的小鼠中,不再观察到顶端定向的胶原偏移。这些结果突出了基于tectin的基质和上皮信号对盖膜中精确胶原组织的重要性。

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