Tsukushi is a small, leucine-rich repeat proteoglycan that interacts with and regulates essential cellular signaling cascades in the chick retina and murine subventricular zone, hippocampus, dermal hair follicles, and the cochlea. However, its function in the vestibules of the inner ear remains unknown. Here, we investigated the function of Tsukushi in the vestibules and found that Tsukushi deficiency in mice resulted in defects in posterior semicircular canal formation in the vestibules, but did not lead to vestibular hair cell loss. Furthermore, Tsukushi accumulated in the non-prosensory and prosensory regions during the embryonic and postnatal developmental stages. The downregulation of Tsukushi altered the expression of key genes driving vestibule differentiation in the non-prosensory regions. Our results indicate that Tsukushi interacts with Wnt2b, bone morphogenetic protein 4, fibroblast growth factor 10, and netrin 1, thereby controlling semicircular canal formation. Therefore, Tsukushi may be an essential component of the molecular pathways regulating vestibular development.

Tsukushi 是一种小的、富含亮氨酸的重复蛋白多糖，可与小鸡视网膜和小鼠脑室下区、海马、真皮毛囊和耳蜗中的基本细胞信号级联反应并对其进行调节。然而，其在内耳前庭中的功能仍然未知。在这里，我们研究了前庭中筑紫的功能，发现小鼠的筑紫缺乏导致前庭后半规管形成缺陷，但并未导致前庭毛细胞丢失。此外，在胚胎和出生后发育阶段，Tsukushi 在非感觉和感觉区域积累。Tsukushi 的下调改变了驱动非感觉区前庭分化的关键基因的表达。我们的结果表明，Tsukushi 与Wnt2b、骨形态发生蛋白 4、成纤维细胞生长因子 10 和 netrin 1，从而控制半规管形成。因此，Tsukushi 可能是调节前庭发育的分子途径的重要组成部分。