Manipulating cell fate in the cochlea: A feasible therapy for hearing loss

Mammalian auditory hair cells do not spontaneously regenerate, unlike hair cells in lower vertebrates, including fish and birds. In mammals, hearing loss due to the loss of hair cells is permanent and intractable. Recent studies in the mouse have demonstrated spontaneous hair cell regeneration during a short postnatal period, but this regenerative capacity is lost in the adult cochlea. Reduced regeneration coincides with a transition that results in a decreased pool of progenitor cells in the cochlear sensory epithelium. Here, we review the signaling cascades involved in hair cell formation and morphogenesis of the organ of Corti in developing mammals, the changing status of progenitor cells in the cochlea, and the regeneration of auditory hair cells in adult mammals.