heparitin-sulfate and sphingosine-kinase

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.

Topics: Animals; Axons; Embryo, Nonmammalian; Enzyme Activation; Gene Expression Regulation, Developmental; Growth Cones; Heparitin Sulfate; Humans; Lim Kinases; Lysophospholipids; Mice; Phosphotransferases (Alcohol Group Acceptor); Proteasome Inhibitors; Receptors, Lysosphingolipid; Retina; rhoA GTP-Binding Protein; Signal Transduction; Sphingosine; Visual Pathways; Xenopus laevis