Neurobiology Select

The generation of diverse types of nerve cells and the establishment and sculpting of synaptic connections between neurons form the basis for building a functional nervous system. This Neurobiology Select highlights recent findings that yield new insights into the differentiation of progenitor cells into neurons, the development of dendrites, and neuronal connectivity. 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, Carlé 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. Whereas Notch signaling is capable of limiting the differentiation potential of cells in the mature mammalian brain, it seems to play a distinctly different role in the developing nervous system. During development, neural precursor cells in the mammalian nervous system first give rise to neurons before becoming competent to differentiate into glial cells such as astrocytes. As the relative proportion of neurons to glia in the nervous system may directly impact neural function, one intriguing candidate for inducing the switch to gliogenesis is the newly differentiated neuron itself. Namihira et al. (2009) now report evidence suggesting that committed neuronal precursor cells and young neurons may activate Notch signaling in the remaining neural …