| The newt, Notopthalmus viridescens is one of the few tetrapod vertebrates capable of extensive regeneration of the central nervous system, however, the factors involved in this process are still unknown. Chemokine signalling through the receptor CXCR4, has been found to be involved in the development of the central nervous system of mammals and more recently in epimorphic fin regeneration in zebrafish. We have hypothesized that the CXCR4 signalling pathway is involved in spinal cord and tail regeneration in the adult newt, possibly as a downstream target of retinoic acid signalling. We found that CXCR4 mRNA expression was observed in the brain, spinal cord, heart, gut, liver and regenerating tail blastemas. CXCR4 expression increased over the first 12 days of tail regeneration and returned to basal expression levels at day 21 of regeneration. Inhibition of CXCR4 with AMD3100, a specific receptor antagonist, led to a decrease in CXCR4 mRNA in the regenerating tail 14 days post amputation. Histological analysis suggests a delay in the early stages of tail and spinal cord regeneration. Spinal cord explants treated with CXCL12, the ligand to CXCR4, displayed enhanced neurite outgrowth in vitro. Explants treated with AMD3100 abolished any retinoic acid enhanced neurite outgrowth effects suggesting a link between these signalling pathways. |
