Glial cells generate neurons--master control within CNS regions: developmental perspectives on neural stem cells

A common problem in neural stem cell research is the poor generation of neuronal or oligodendroglial descendants. The author takes a developmental perspective to propose solutions to this problem. After a general overview of the recent progress in developmental neurobiology, she highlights the necessity of the sequential and hierarchical specification of CNS precursors toward the generation of specific cell types, for example, neurons. In the developing as well as the adult CNS, multipotent stem cells do not directly generate neurons but give rise to precursors that are specified and restricted toward the generation of neurons. Some molecular determinants of this fate restriction have been identified during recent years and reveal that progression via this fate-restricted state is a necessary step of neurogenesis. These discoveries also demonstrate that neuronal fate specification is inseparably linked at the molecular level to regionalization of the developing CNS. These fate determinants and their specific action in distinct region-specific contexts are essential to direct the progeny of stem cells more efficiently toward the generation of the desired cell types. Recent data are discussed that demonstrate the common identity of precursors and stem cells in the developing and adult nervous system as radial glia, astroglia, or non-myelinating glia. A novel lineage model is proposed that incorporates these new views and explains why the default pathway of stem cells is astroglia. These new insights into the cellular and molecular mechanisms of neurogenesis help to design novel approaches for reconstitutive therapy of neurodegenerative diseases.