Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse.
Abstract
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.
1 Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105; Hearing Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, United Kingdom;
2 F. M. Kirby Neurobiology Center, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115; Departments of Neurology and Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109; and.
3 Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105;
4 F. M. Kirby Neurobiology Center, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115;
5 Solomon H. Snyder Department of Neuroscience, John Hopkins University School of Medicine, Baltimore, MD 21205.
6 Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105
7 F. M. Kirby Neurobiology Center, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115; Departments of Neurology and Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109; and Otology and Laryngology, Harvard Medical School, Boston, MA 02115