Notch signaling and the emergence of auditory hair cells

Objective: Recent insights into the mechanisms that determine a hair cell's fate have emerged from studies on invertebrate sensory organs and the avia n inner ear. These mechanisms have important implications for our understan ding of the possible therapeutic management of sensorineural deafness. This article reviews the current state of our knowledge regarding mammalian aud itory hair cell fate specification. Design: Data were obtained from the MEDLINE database and data presented at the Molecular Biology of Hearing and Deafness Meeting (Bethesda, Md, Octobe r 1998). Articles reporting information about cell fate specification and N otch and its ligands were selected. Main Outcome Measures: Data pertaining to cell fate mechanisms, Notch and i ts ligands, and application to hearing were extracted. Results: The Notch/ligand mechanism is responsible for the specification of the hair cell phenotype. Conclusions: Major progress has been made in understanding this fundamental process, and its application to hair cell determination is only now being realized. Possible applications could involve the "switching" of supporting cells to hair cells, thus replenishing those hair cells damaged in sensori neural hearing loss.