Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse
Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse
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DOI：
10.1073/pnas.1408064111
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发表时间：
2014-11-25
影响因子：
11.1
通讯作者：
Corfas, Gabriel
中科院分区：
文献类型：
--
作者：
Lagarde, Marcia M. Mellado;Wan, Guoqiang;Corfas, Gabriel
耳蜗中的支持细胞在感觉毛细胞和听觉神经元的发育、维持和功能中发挥着关键作用。尽管毛细胞或听觉神经元的损失会导致感音神经性听力损失，但支持细胞损失对听觉功能的影响在很大程度上尚不清楚。在这项研究中，我们专门消融了内缘细胞（IBC）和内指骨细胞（IPhC），这是小鼠体内围绕内毛细胞（IHC）的两种类型的支持细胞。我们证明 Corti 器官具有在产后早期发育期间有效补充 IBC/IPhC 的内在能力。重新增殖取决于毛细胞和大上皮嵴内细胞的存在，并且与细胞增殖无关。新生儿耳蜗的这种可塑性反应可以保护成年小鼠的神经元存活、传入神经支配和听力敏感性。相比之下，成熟的Corti器官失去了IBC/IPhC再生能力，因此IHC存活和听力敏感性显着受损，表明耳蜗支持细胞再生存在关键时期。我们的研究结果表明，静止的新生儿柯蒂氏器官在体内丧失后可以完全补充特定的支持细胞，以保证成熟的听力功能。
Supporting cells in the cochlea play critical roles in the development, maintenance, and function of sensory hair cells and auditory neurons. Although the loss of hair cells or auditory neurons results in sensorineural hearing loss, the consequence of supporting cell loss on auditory function is largely unknown. In this study, we specifically ablated inner border cells (IBCs) and inner phalangeal cells (IPhCs), the two types of supporting cells surrounding inner hair cells (IHCs) in mice in vivo. We demonstrate that the organ of Corti has the intrinsic capacity to replenish IBCs/IPhCs effectively during early postnatal development. Repopulation depends on the presence of hair cells and cells within the greater epithelial ridge and is independent of cell proliferation. This plastic response in the neonatal cochlea preserves neuronal survival, afferent innervation, and hearing sensitivity in adult mice. In contrast, the capacity for IBC/IPhC regeneration is lost in the mature organ of Corti, and consequently IHC survival and hearing sensitivity are impaired significantly, demonstrating that there is a critical period for the regeneration of cochlear supporting cells. Our findings indicate that the quiescent neonatal organ of Corti can replenish specific supporting cells completely after loss in vivo to guarantee mature hearing function.