Sphingosine 1-phosphate (S1P) signaling is required for maintenance of hair cells mainly via activation of S1P2

Deron R. Herr, Nicolas Grillet, Martin Schwander, Richard Rivera, Ulrich Müller, Jerold Chun

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1474-1478
Number of pages5
JournalJournal of Neuroscience
Volume27
Issue number6
DOIs
StatePublished - Feb 7 2007

Keywords

  • Cochlea
  • GPCR
  • Hair cell
  • Hearing loss
  • Knock-out mice
  • Vestibular

ASJC Scopus subject areas

  • Neuroscience(all)

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