|Budget Amount *help
¥17,200,000 (Direct Cost: ¥17,200,000)
Fiscal Year 2002: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2001: ¥10,600,000 (Direct Cost: ¥10,600,000)
Multipotential neural stem cells serve as the origin of diverse cell types during genesis of the mammalian central nervous system (CNS). During early development, stem cells self-renew and increase their total cell numbers without overt differentiation. At later stages, the cells withdraw from this self-renewal mode, and are fated to differentiate into specific subtypes of neurons and glia in a spatially and temporally regulated manner. However, the molecular mechanisms underlying these processes remain poorly understood. In this study, we have demonstrated that the combinatorial expression and functions of a set of homeodomain-type (Pax6, Nkx2.2, Nkx6.1) and HLH-type (Olig1, Olig2, Ngn1, Ngn2, Ngn3, Mash1, Id1, Id2) play important roles in the patterned and ordered generation of multiple types of neurons and glia in the developing vertebrate central nervous system. Furthermore, we found that the same set of molecules regulate the proliferation and differentiation of neural stem cells in the adult brain and spinal cord. By applying such knowledge, we have also developed strategies to enhance latent regenerative potential of adult neural stem cells, and thereby could induce regeneration of new neurons in damaged tissues. Thus, our study has open a novel avenue of researches that link neural development during embryogenesis and its regeneration in the adult CNS.