Extrinsic and Intrinsic Mechanisms Regulating Neural Stem Cells and Neurogenesis in the Adult Brain
New neurons are continuously generated from adult neural stem/progenitor cells（NSCs) residing inthe subventricular zone of the lateral ventricles and the subgranularzone of the hippocampal dentategyrus in all mammals examined，including humans. Outside of these two neurogenic regions,proliferating NSCs rarely give rise to functio-nal neurons under physiological conditions. Duringactive adult neurogenesis，NSCs generate functional neurons through orchestrated steps，including cellproliferation，fate specification，neuronal migration，axonal and dendritic growth，and finally synapticintegration into the existing circuitry. As in other somatic stem cell syst-ems，neurogenesis from NSCsin the two neurogenic regions of the adult brain is tig-htly regulated by the highly specializedmicroenvironment surrounding the NPCs. The-se “neurogenic niches” not only anatomically houseadult NSCs，but also functiona-lly control their development in vivo. Using multiple approaches forbirth-dating，genetic marking and manipulation of proliferating NSCs and their progeny in the den-tategyrus of adult mice，we have characterized the sequential events of adult neur-ogenesis in vivo. Ourstudies have identified signaling molecules within the uniqueneurogenic niche of the dentate gyrus toeither positively or negatively regulate va-rious aspects of adult neurogenesis in an activity-dependentfashion. In addition t-o extrinsic factors，we have also identified essential intrinsic regulators of adu-ltneurogenesis in vivo，such as Disrupted-in-Schizophrenia 1（DISC1) and NDEL1. Wehope a betterunderstanding of cellular and molecular mechanisms regulating adult ne-ural stem cells andneurogenesis may lead to novel strategies for functional neuron-al replacement therapy after injury ordegenerative neurological diseases.
神经调节 神经干细胞 神经元迁移 轴突生长
Hongjun Song
Institute for Cell Engineering, Department of Neurology and Neuroscience, Johns Hopkins University School of Medicine
国内会议
长沙
英文
303-304
2008-07-25（万方平台首次上网日期，不代表论文的发表时间）