A role for S1P signalling in axon guidance in the Xenopus visual system.
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.
Strochlic
Laure
L
Department of Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Dwivedy
Asha
A
van Horck
Francisca P G
FP
Falk
Julien
J
Holt
Christine E
CE
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020439:Growth Cones / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D061988:Proteasome Inhibitors; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014795:Visual Pathways / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099157:Sphingosine Kinase
D006497:Heparan Sulfate; D054461:Lim Kinases; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D061988:Proteasome Inhibitors; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D020742:rhoA GTP-Binding Protein; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate