Stone Jennifer S, Pujol Rémy, Nguyen Tot Bui, Cox Brandon C
Department of Otolaryngology-Head and Neck Surgery and the Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195-7923.
Institut National de la Santé et de la Recherche Médicale Unit 1051, Institute of Neuroscience, University of Montpellier, 34000 Montpellier, France.
J Neurosci. 2021 Jul 21;41(29):6217-6233. doi: 10.1523/JNEUROSCI.1831-20.2021.
The sense of balance relies on vestibular hair cells, which detect head motions. Mammals have two types of vestibular hair cell, I and II, with unique morphological, molecular, and physiological properties. Furthermore, each hair cell type signals to a unique form of afferent nerve terminal. Little is known about the mechanisms in mature animals that maintain the specific features of each hair cell type or its postsynaptic innervation. We found that deletion of the transcription factor from Type II hair cells in adult mice of both sexes caused many cells in utricles to acquire features unique to Type I hair cells and to lose Type II-specific features. This cellular transdifferentiation, which included changes in nuclear size, chromatin condensation, soma and stereocilium morphology, and marker expression, resulted in a significantly higher proportion of Type I-like hair cells in all epithelial zones. Furthermore, deletion from Type II hair cells triggered non-cell autonomous changes in vestibular afferent neurons; they retracted bouton terminals (normally present on only Type II cells) from transdifferentiating hair cells and replaced them with a calyx terminal (normally present on only Type I cells). These changes were accompanied by significant expansion of the utricle's central zone, called the striola. Our study presents the first example of a transcription factor required to maintain the type-specific hair cell phenotype in adult inner ears. Furthermore, we demonstrate that a single genetic change in Type II hair cells is sufficient to alter the morphology of their postsynaptic partners, the vestibular afferent neurons. The sense of balance relies on two types of sensory cells in the inner ear, Type I and Type II hair cells. These two cell types have unique properties. Furthermore, their postsynaptic partners, the vestibular afferent neurons, have differently shaped terminals on Type I versus Type II hair cells. We show that the transcription factor Sox2 is required to maintain the cell-specific features of Type II hair cells and their postsynaptic terminals in adult mice. This is the first evidence of a molecule that maintains the phenotypes of hair cells and, non-cell autonomously, their postsynaptic partners in mature animals.
平衡感依赖于前庭毛细胞，前庭毛细胞可检测头部运动。哺乳动物有两种类型的前庭毛细胞，即I型和II型，它们具有独特的形态、分子和生理特性。此外，每种毛细胞类型向一种独特形式的传入神经末梢发送信号。对于成熟动物中维持每种毛细胞类型及其突触后神经支配的特定特征的机制，人们了解甚少。我们发现，在成年雌雄小鼠的II型毛细胞中删除转录因子，导致许多椭圆囊中的细胞获得了I型毛细胞特有的特征，并失去了II型特异性特征。这种细胞转分化，包括核大小、染色质凝聚、胞体和静纤毛形态以及标志物表达的变化，导致所有上皮区域中I型样毛细胞的比例显著更高。此外，从II型毛细胞中删除转录因子引发了前庭传入神经元的非细胞自主性变化；它们从转分化的毛细胞中缩回终扣末端（通常仅存在于II型细胞上），并用花萼末端（通常仅存在于I型细胞上）取代它们。这些变化伴随着椭圆囊中央区域（称为条纹区）的显著扩大。我们的研究展示了在成年内耳中维持特定类型毛细胞表型所需的转录因子的首个实例。此外，我们证明II型毛细胞中的单一基因变化足以改变其突触后伙伴前庭传入神经元的形态。平衡感依赖于内耳中的两种感觉细胞，即I型和II型毛细胞。这两种细胞类型具有独特的特性。此外，它们的突触后伙伴前庭传入神经元在I型和II型毛细胞上具有不同形状的末端。我们表明，转录因子Sox2是成年小鼠中维持II型毛细胞及其突触后末端的细胞特异性特征所必需的。这是首个证明在成熟动物中维持毛细胞表型及其突触后伙伴的非细胞自主性分子的证据。
