Reelin affects chain-migration and differentiation of neural precursor cells

In the adult mammalian brain, multipotential neural stem cells (NSC) persist throughout life in areas where neurogenesis is maintained. A distinctive trait of NSCs growing in vitro as neurospheres (NS), is their ability to self-renew, differentiate and migrate to sites of injury, such as gliomas. We have studied the role of Reelin, an extracellular matrix protein involved in brain development, in NSCs derived from normal newborn mice or from reeler, a natural mutant in which Reelin is not expressed. We show that the absence of Reelin negatively affects proliferation, NS-forming ability, and neuronal differentiation. Reeler NSCs are unable to migrate in chains, a migration mode typical of neural precursors homing to injury sites in adult CNS. All these effects are partially rescued by ectopic Reelin supplementation. Finally, we show that reeler NSCs fail to migrate in vivo towards gliomas. Overall, our results indicate that Reelin affects all major features of postnatal NSCs, and that it is required for the proper homing of NSCs to tumor sites in adult brain.