CXC chemokine receptor 4 regulates neuronal migration and axonal pathfinding in the developing nervous system: implications for neuronal regeneration in the adult brain

Chemotactic cytokines (chemokines) are small secreted proteins that control leukocyte trafficking in immune organs. Chemokines which are induced in the brain during conditions of inflammation play a role in the local immune response. Recently, it has been established in the rodent brain that distinct chemokines and chemokine receptors are constitutively expressed by neurons and that these chemokines modulate neuronal functions. The CXC motif chemokine stromal cell-derived factor-1 (SDF-1), CXCL12 together with its cognate receptor CXCR4 represents the best-characterized neuronal chemokine system. Transwell migration assays with neuronal precursors, pharmacological manipulation of CXCR4 signaling in embryonic brain explants, and histochemical studies of SDF-1- or CXCR4-deficient mouse embryos provide proof that SDF-1 directs neuronal migration and axonal pathfinding in the developing nervous system. In the adult brain, SDF-1 is thought to influence neurogenesis as well as recruitment of brain resident and non-resident circulating cells toward sites of lesion. The present review summarizes patterns and functions of the SDF-1/CXCR4 system in the rodent brain with a focus on the developing and adult cerebral cortex.