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The Journal of Neuroscience, February 7, 2007, 27(6):1474-1478; doi:10.1523/JNEUROSCI.4245-06.2007

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Brief Communications
Sphingosine 1-Phosphate (S1P) Signaling Is Required for Maintenance of Hair Cells Mainly via Activation of S1P₂

Deron R. Herr,¹ Nicolas Grillet,² Martin Schwander,² Richard Rivera,¹ Ulrich Müller,² and Jerold Chun¹

¹Department of Molecular Biology, Helen L. Dorris Institute for Neurological and Psychiatric Disorders, and ²Department of Cell Biology, Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, California 92037

Correspondence should be addressed to Jerold Chun, Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Email: jchun{at}scripps.edu

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.

Key words: GPCR; hair cell; hearing loss; cochlea; vestibular; knock-out mice

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Received Sept. 28, 2006; revised Jan. 5, 2007; accepted Jan. 6, 2007.

Correspondence should be addressed to Jerold Chun, Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Email: jchun{at}scripps.edu

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