Regulatory mechanisms underlying the neurogenesis-to-gliogenesis switch by neural stem cells

During development of the vertebrate central nervous system (CNS), neural stem cells (NSCs) fi rst generate neurons, followed by glia. This sequential production of specifi c cell types is advantageous for the organism, since glia play pivotal roles in the maintenance and function of neurons and also, under some conditions, in the inhibition of axonal growth. The latter may be related to the conservation of the newly established neuronal circuitry. The temporal regulation of stem cell differentiation is captivating, given that the loss of stem cell plasticity is often part of the standard mammalian aging process. The reduced plasticity of adult stem cells, including NSCs, directly affects the capacity of the metazoan to regenerate lost or damaged neural tissue and seems to have occurred over the course of evolution. Indeed, the injured adult mammalian brain is scarcely capable of regeneration, not only due to the limited number of adult NSCs but also because of their low neurogenic capacity, except for in certain restricted CNS regions. By contrast, some lower vertebrates (e.g., red-spotted newts) show high regenerative capacity in the brain, with the effi cient induction of neurogenesis after injury. Therefore, addressing the regulatory mechanisms underlying the neurogenesis-to-gliogenesis switch by NSCs during development is critical to understanding the restricted plasticity of the adult mammalian CNS. Accordingly, this chapter will review the recent progress in the fi eld of NSC biology, especially re arding the temporal regulation of neurogenesis and gliogenesis.