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First published online 12 December 2007
doi: 10.1242/dev.009563

Development 135, 333-342 (2008)
Published by The Company of Biologists 2008
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A role for S1P signalling in axon guidance in the Xenopus visual system

Laure Strochlic, Asha Dwivedy, Francisca P. G. van Horck, Julien Falk and Christine E. Holt*

Department of Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

* Author for correspondence (e-mail: ceh{at}mole.bio.cam.ac.uk)

Accepted 17 October 2007

Sphingosine 1-phosphate (S1P), a lysophospholipid, plays an important chemotactic role in the migration of lymphocytes and germ cells, and is known to regulate aspects of central nervous system development such as neurogenesis and neuronal migration. Its role in axon guidance, however, has not been examined. We show that sphingosine kinase 1, an enzyme that generates S1P, is expressed in areas surrounding the Xenopus retinal axon pathway, and that gain or loss of S1P function in vivo causes errors in axon navigation. Chemotropic assays reveal that S1P elicits fast repulsive responses in retinal growth cones. These responses require heparan sulfate, are sensitive to inhibitors of proteasomal degradation, and involve RhoA and LIM kinase activation. Together, the data identify downstream components that mediate S1P-induced growth cone responses and implicate S1P signalling in axon guidance.

Key words: Sphingosine 1-phosphate, Retinal ganglion cell, Axon pathfinding, Growth cone, Collapse, Guidance cue


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© The Company of Biologists Ltd 2008