Migration and differentiation of neural precursor cells can be directed by microglia

Recent reports have supported the existence of neural stem cells in the adult mammalian CNS. Important features of such cells are self-renewal and multipotency, i.e., they can give rise to neurons, astrocytes, and oligodendrocytes and thus in principle replace lost cells in the CNS. Observations in several animal models of CNS diseases have shown that by unknown mechanisms endogenous as well as exogenous precursor cells preferentially migrate to damaged areas. Microglia are immunoreactive cells of nonneural lineage resident in the CNS. After injury to the CNS, microglia are rapidly activated and found concentrated at the sites of injury. In the present article we show, in two different assays, that soluble factors released from mouse microglial cells direct the migration of neural CNS precursor cells. We also provide evidence that microglia have the capacity to influence the differentiation of both adult and embryonic neural precursor cells toward a neuronal phenotype. Given that an invariant feature of pathological processes in CNS is the activation of microglia, these results indicate an important and unique role for microglia in directing the replacement of damaged or lost cells in the CNS.