RT Journal Article SR Electronic T1 Sphingosine 1-Phosphate (S1P) Signaling Is Required for Maintenance of Hair Cells Mainly via Activation of S1P2 JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1474 OP 1478 DO 10.1523/JNEUROSCI.4245-06.2007 VO 27 IS 6 A1 Deron R. Herr A1 Nicolas Grillet A1 Martin Schwander A1 Richard Rivera A1 Ulrich Müller A1 Jerold Chun YR 2007 UL http://www.jneurosci.org/content/27/6/1474.abstract AB Hearing requires the transduction of vibrational forces by specialized epithelial cells in the cochlea known as hair cells. The human ear contains a finite number of terminally differentiated hair cells that, once lost by noise-induced damage or toxic insult, can never be regenerated. We report here that sphingosine 1-phosphate (S1P) signaling, mainly via activation of its cognate receptor S1P2, is required for the maintenance of vestibular and cochlear hair cells in vivo. Two S1P receptors, S1P2 and S1P3, were found to be expressed in the cochlea by reverse transcription-PCR and in situ hybridization. Mice that are null for both these receptors uniformly display progressive cochlear and vestibular defects with hair cell loss, resulting in complete deafness by 4 weeks of age and, with complete penetrance, balance defects of increasing severity. This study reveals the previously unknown role of S1P signaling in the maintenance of cochlear and vestibular integrity and suggests a means for therapeutic intervention in degenerative hearing loss.