CXCL12-Mediated Murine Neural Progenitor Cell Movement Requires PI3Kβ Activation

The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110 alpha and p110 beta in NPC, only p110 beta participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110 beta blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110 beta is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110 beta is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex.