Heffer Alison, Lee Choongheon, Mayernik Joseph P, Holt Joseph C, Kiernan Amy E
Flaum Eye Institute, Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York 14642.
Departments of Otolaryngology, University of Rochester, Rochester, New York 14642.
J Neurosci. 2025 Feb 26;45(9):e1365242024. doi: 10.1523/JNEUROSCI.1365-24.2024.
The inner ear houses both hearing and balance sensory modalities. The hearing and balance organs consist of similar cell types, including sensory hair cells and associated supporting cells. Previously we showed that is required for maintaining supporting cell survival during cochlear maturation. To understand the role of Notch during vestibular maturation, we deleted from the vestibular organs of both male and female mice at birth. Histological analyses showed a reduction of supporting cells accompanied by an increase in type II hair cells, indicating a conversion of supporting cells to hair cells. Analysis of mature sensory organs indicate the converted hair cells survive, despite a severe reduction of supporting cells. Vestibular sensory evoked potentials (VsEPs), thought to be generated within the striola regions of the maculae, were absent, indicating that NOTCH1 is critical for striolar function. Specialized type I hair cells in the striola failed to develop the complex calyces typical of these cells. mutants did not exhibit vestibular behaviors such as circling and head shaking but showed difficulties with tests of balance and swimming. These results indicate that, unlike the cochlea, supporting cells in balance organs retain the plasticity to convert to hair cells which can survive into adulthood. Despite hair cell survival, vestibular function is compromised likely due to the loss of supporting cells and altered innervation.
内耳包含听觉和平衡两种感觉模式。听觉和平衡器官由相似的细胞类型组成，包括感觉毛细胞和相关的支持细胞。之前我们表明，在耳蜗成熟过程中， 对于维持支持细胞的存活是必需的。为了了解Notch在前庭成熟过程中的作用，我们在出生时从雄性和雌性小鼠的前庭器官中删除了 。组织学分析显示支持细胞减少，同时II型毛细胞增加，表明支持细胞向毛细胞转化。对成熟感觉器官的分析表明，尽管支持细胞严重减少，但转化后的毛细胞仍能存活。前庭感觉诱发电位（VsEPs）被认为是在黄斑的纹区产生的，但未检测到，这表明NOTCH1对纹区功能至关重要。纹区特化的I型毛细胞未能发育出这些细胞典型的复杂杯状突触。 突变体没有表现出如转圈和摇头等前庭行为，但在平衡和游泳测试中表现出困难。这些结果表明，与耳蜗不同，平衡器官中的支持细胞保留了转化为毛细胞并存活至成年的可塑性。尽管毛细胞存活，但前庭功能可能由于支持细胞的丧失和神经支配的改变而受损。
