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.

中文翻译：

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Tsukushi对内耳的发育至关重要。

Tsukushi（TSK）-一种小的，分泌的，富含亮氨酸的重复蛋白聚糖，与必需的细胞信号传导级联反应并对其进行调节。但是，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显示，小鼠中的TSK缺乏会导致内部毛细胞中形成异常的纤毛和听力损失，但不会导致这些细胞的损失。TSK在胚胎早期的非感觉区域和胚胎后期的非感觉区域和感觉区域中积累。在成年小鼠中，TSK位于Corti，螺旋神经节细胞和血管纹中。此外，TSK的丢失导致关键基因表达的动态变化，从而驱动内感毛细胞在感觉区域内分化。最后，我们的结果表明TSK与Sox2和BMP4相互作用，以控制内部毛细胞中的纤毛形成。因此，TSK似乎是调节内耳发育的分子途径的重要组成部分。