The role of CXCL12, its receptors and signaling pathways in axonal regeneration in the central nervous system

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Neurons of the central nervous system (CNS) normally fail to regenerate injured axons. This regenerative failure is due to inhibitory molecules of the CNS myelin and glial scar forming at the injury site as well as an insufficient intrinsic capability of mature neurons to regrow axons. As shown by our published and unpublished data CXCL12 enhances axon growth of primary neurons and exerts disinhibitory effects, resulting in enhanced axon growth after spinal cord injury. However, the mechanisms underlying these beneficial effects of CXCL12 are still un-known. This grant proposal addresses this issue by identifying the functional receptor(s), the critical downstream signaling pathways, and subcellular sites of CXCL12 interaction. Moreover, we will test the potential of CXCL12 as a factor promoting axonal regeneration in the injured optic nerve. This research proposal involves pharmacological as well as genetic approaches and uses cell culture models and two in vivo regeneration paradigms.