Noda Teppei, Wakizono Takahiro, Manabe Takahiro, Aoyagi Kei, Kubota Marie, Yasui Tetsuro, Nakagawa Takashi, Nakashima Kinichi, Meno Chikara
Department of Otolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 8128582, Japan.
Department of Otolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 8128582, Japan; Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 8128582, Japan.
Hear Res. 2025 Jun;462:109282. doi: 10.1016/j.heares.2025.109282. Epub 2025 Apr 19.
The regenerative capacity of inner ear hair cells in mammals varies between the cochlea and the vestibular system. Hair cells in the cochlea lack regenerative ability, whereas those in the vestibular system exhibit limited regenerative potential. However, supporting cells in the cochlea retain proliferative capacity, making them a key focus in auditory regeneration research. Similarly, spiral ganglion neurons actively proliferate until birth but lose this ability within a week postnatally, sharing the regenerative limitations of hair cells. This study investigated the role of the canonical Wnt signaling pathway as a potential regulator of these cells. Wnt signaling plays a crucial role in otic development and inner ear morphogenesis. Using reporter mice, we analyzed the activity of the Wnt canonical pathway in the inner ear at the cellular stages from embryonic to adult stages, assessing fluorescence intensities as an indicator of signaling activity. Our findings demonstrate that Wnt signaling remains active in the vestibular hair cells and in the supporting cells of both the cochlea and vestibule throughout development and into adulthood. In addition, Wnt activity was observed in spiral ganglion neurons up to 7 days after birth, coinciding with their period of proliferative potential. These findings suggest that Wnt signaling is integral to cell proliferation in the inner ear both before and after birth.
哺乳动物内耳毛细胞的再生能力在耳蜗和前庭系统之间存在差异。耳蜗中的毛细胞缺乏再生能力，而前庭系统中的毛细胞则表现出有限的再生潜力。然而，耳蜗中的支持细胞保留了增殖能力，使其成为听觉再生研究的关键焦点。同样，螺旋神经节神经元在出生前会积极增殖，但在出生后一周内失去这种能力，与毛细胞具有相同的再生限制。本研究调查了经典Wnt信号通路作为这些细胞潜在调节因子的作用。Wnt信号在耳发育和内耳形态发生中起着关键作用。我们使用报告基因小鼠，分析了从胚胎期到成年期细胞阶段内耳中Wnt经典通路的活性，将荧光强度作为信号活性的指标进行评估。我们的研究结果表明，在整个发育过程直至成年期，Wnt信号在前庭毛细胞以及耳蜗和前庭的支持细胞中均保持活跃。此外，在出生后7天内的螺旋神经节神经元中观察到Wnt活性，这与它们的增殖潜力期相吻合。这些发现表明，Wnt信号在出生前后的内耳细胞增殖中都是不可或缺的。
