Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 47; pp. 16919 - 16924
• Main Authors: Lagarde, Marcia M. Mellado, Wan, Guoqiang, Zhang, LingLi, Gigliello, Angelica R., McInnis, John J., Zhang, Yingxin, Bergles, Dwight, Zuo, Jian, Corfas, Gabriel
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.11.2014; National Acad Sciences
• Subjects: Animals; Animals, Newborn; Biological Sciences; Cells; Cochlea; Cochlea - physiology; Deafness; Ears & hearing; Epithelium; Hair cells; Hearing; Inner ear; Inner hair cells; Mice; Neuroscience; Organ of corti; Regeneration; Rodents; Sensitivity; Stem cells; cell ablation; deafness; glia; hair cell; organ of Corti
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1408064111

Significance The auditory sensory epithelium contains two major cell types: hair cells and supporting cells. Mammalian auditory hair cells do not regenerate after damage or loss, resulting in permanent hearing impairment. How supporting cell loss affects auditory function remains to be determined. Here, we demonstrate that inner border and inner phalangeal cells, the two types of supporting cells surrounding inner hair cells, can be replenished completely after selective ablation in the neonatal cochlea, allowing hearing to be preserved. Our findings challenge the view that mammalian auditory sensory epithelium has limited intrinsic regenerative capacity and provide previously unindetified opportunities for replacement of damaged auditory cells and restoration of hearing. 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.