Tuesday, 24 March 2009 15:01
Neural stem cells give rise to new neurons in the adult mammalian brain. Forebrain ependymal cells lining the lateral ventricles have been proposed as a candidate neural stem cell, although some studies suggest that they are quiescent and terminally differentiated.
In a recent study, Carle´ n et al. (2009) report that these ciliated neuroepithelial cells do not normally contribute to adult neurogenesis, but that they can give rise to neurons and astrocytes after a stroke. The authors take advantage of a virus-based lineage-mapping technique to mark ependymal cells in the adult mouse brain and their progeny by b-galactosidase expression. They find that in wild-type mice, b-galactosidase expression is restricted to ependymal cells, indicating that the cells do not give rise to neuronal progeny. However, when the mice suffer a stroke, the layer of ependymal cells becomes disordered and after 2 weeks is severely depleted. Meanwhile, there is a corresponding increase in ependymal cell-derived neuroblasts and astrocytes, some of which migrate into the subventricular zone. The authors find that Notch signaling activated by the protein RBP-J maintains ependymal cells in a quiescent fate. Blocking expression of RBP-J in ependymal cells enables them to enter the cell cycle, migrate, and differentiate into neurons. The ability of ependymal cells to become neuroblasts and astrocytes after brain injury suggests the
exciting possibility that populations other than neural stem cells may be able to contribute to brain repair after severe injury.
Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.
Article link: M. Carle´n et al. (2009). Nat. Neurosci. 12, 259–267.