More than just supporting: new insights into the roles of supporting cells in the postnatal and adult inner ear

CORFAS G; LIBERMAN MC; GOMEZ CASATI, ME; MURTIE J; RIO C; STANKOVIC, K; SUGAWARA, M

Congreso; 8th Molecular Biology of Hearing and Deafness Conferenc; 2011

While it is clear that, during embryonic development, supporting cells of inner ear sensory epithelia serve as hair-cell precursors, the roles of these non-neuronal cells in the postnatal and adult periods remain poorly understood. We are using genetically modified mice to investigate the post-natal roles of supporting cells and the molecules that mediate them. Our studies show that supporting cells are critical for the formation and maintenance of vestibular and cochlear inner hair cell synapses and for the long-term survival of spiral ganglion neurons (SGNs). I will present our data showing that BDNF produced by supporting cells is critical for synapse development/maintenance in the vestibular system, while supporting cell-derived NT3 plays similar roles in the cochlea. Expression of BDNF and NT3 is regulated by the NRG1/ErbB signaling pathway, pointing to reciprocal trophic interactions between sensory neurons and supporting cells in the formation and maintenance of a functional sensory epithelium. I will also discuss our studies on the roles of supporting cells in long-term survival of SGNs.The prevailing idea that inner hair cells (IHCs) are the key source of factors that maintain SGN survival is primarily based on the observation that IHC loss, by acoustic trauma or ototoxic drugs, leads to significant delayed loss of SGNs. Our recent studies show that IHC loss by non-traumatic means does not affect neuronal survival, whereas mice in which supporting cells are defective in ErbB signaling leads to loss of SGNs even in the absence of IHC loss. Together, these studies show that supporting cells are actively engaged in the promotion of maturation, function and maintenance of the inner ear and that this is, at least in part, mediated by reciprocal trophic interactions between neuronal and non-neuronal cells.