Tsukushi is essential for the development of the inner ear
Tsukushi is essential for the development of the inner ear
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DOI：
10.1186/s13041-020-00570-z
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发表时间：
2020-03-03
期刊：
影响因子：
3.6
通讯作者：
Minoda, Ryosei
中科院分区：
文献类型：
--
作者：
Miwa, Toru;Ohta, Kunimasa;Minoda, Ryosei
Tsukushi (TSK) 是一种小的、分泌的、富含亮氨酸的重复蛋白聚糖，与重要的细胞信号级联相互作用并调节。然而，其在小鼠内耳中的功能尚不清楚。在这项研究中，对听觉脑干反应、荧光显微镜和扫描电子显微镜的测量表明，小鼠的 TSK 缺陷会导致内毛细胞中异常静纤毛的形成和听力损失，但不会导致这些细胞的损失。 TSK在早期胚胎阶段在非前感觉区域积累，在胚胎晚期在非前感觉和前感觉区域积累。在成年小鼠中，TSK 定位于柯蒂氏器、螺旋神经节细胞和血管纹。此外，TSK 的缺失导致关键基因表达的动态变化，这些基因驱动前感觉区域内毛细胞的分化。最后，我们的结果表明 TSK 与 Sox2 和 BMP4 相互作用来控制内毛细胞中静纤毛的形成。因此，TSK 似乎是调节内耳发育的分子途径的重要组成部分。
Tsukushi (TSK)-a small, secreted, leucine-rich-repeat proteoglycan-interacts with and regulates essential cellular signaling cascades. However, its functions in the mouse inner ear are unknown. In this study, measurement of auditory brainstem responses, fluorescence microscopy, and scanning electron microscopy revealed that TSK deficiency in mice resulted in the formation of abnormal stereocilia in the inner hair cells and hearing loss but not in the loss of these cells. TSK accumulated in nonprosensory regions during early embryonic stages and in both nonprosensory and prosensory regions in late embryonic stages. In adult mice, TSK was localized in the organ of Corti, spiral ganglion cells, and the stria vascularis. Moreover, loss of TSK caused dynamic changes in the expression of key genes that drive the differentiation of the inner hair cells in prosensory regions. Finally, our results revealed that TSK interacted with Sox2 and BMP4 to control stereocilia formation in the inner hair cells. Hence, TSK appears to be an essential component of the molecular pathways that regulate inner ear development.