The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons

Recent data have shown that the chemokine SDF-1 plays a critical role in several aspects of brain development such as cell migration and axon pathfinding. However, its potential function in the generation of axons and dendrites is poorly characterized. In order to better understand the role of SDF-1 in the development of central neurons, we studied the cellular distribution of the SDF-1 receptor CXCR4 by immunocytochemistry of developing hippocampal neurons and tested the effect of SDF-1 in process patterning at the early stages of neuronal development. We found that CXCR4 immunoreactivity undergoes a striking redistribution during development. At the early stages, from day 2 to day 4 in culture, CXCR4 is particularly concentrated at the leading edge of growing neurites. As the cells mature, staining declines at the tip of the processes and becomes more broadly distributed along axons and, to a lesser extent, dendrites. SDF-1 stimulation of neurons at day 1-2 in culture triggers several effects on neuronal morphogenesis. SDF-1 reduces growth cone number and axonal outgrowth but stimulates axonal branching. These latter two effects are not observed in other neurites. This study unravels a new role for SDF-1/CXCR4 in specifying hippocampal neuron morphology by regulating axonal patterning at an early stage of neuronal development.