Development of NSCs

11 2 NATURE| VOL 414 | 1 NOVEMBER 2001 | www.nature.com T he discovery of neural stem cells was rooted in classic studies of haematopoiesis and of invertebrate neural development, which inspired examination of single neural progenitor cells. (In this review, I will use the term ‘progenitor cell’ to refer to all classes of immature, proliferating cells. Neural stem cells are a subtype of progenitor cells in the nervous system that can self-renew and generate both neurons and glia.) The early studies led to the isolation of stem-like cells from the embryonic mammalian central nervous system (CNS) 1–4 and the peripher al nervous sys tem (PN S ) 5 . Since then, stem cells have been isolated from many regions of the embryonic nervous system, indicating th eir ub iquity (Fig. 1a). Af ter the discovery of neural stem cells in the embryo, the first isola tion of stem-like cells from adult brain 6,7 began yet anoth er chapter o f neuroscience. A dult n eural stem cell s have now been found in the two principal adult neurogenic regions, the hippocampus and the subve ntr icular z one (SVZ), and in some non -neuro genic regions, including spinal cord 8–10 (Fig. 1a). These pioneering studies provided a cellular mechanism for adult neurogenesis, which was well-established in birds and becoming accepted in mammals, and raised the possibility that the most intractable of tissues — the CNS — might have regenerative powers. Markers that define CNS s tem cells are only now being developed 11–14 . Hence, they are usu ally identified retro spec- tively on the basis of their behaviour after isolation. In adherent cultures, CNS stem cells produce large clones contain ing neur ons, glia and more stem cells ; they can also be cultured as fl oating, mu lticel lular neuro spheres 8–10 . PNS neur al cres t stem cells e xpress the low-af finity neurot roph in receptor p75 (ref. 5), and grow as adheren t clones contain- ing peripheral neurons and glia, smooth muscle cells and more stem cell s 15 . This review summ arizes w hat we curr ently know abou t stem cells in the devel opin g nervous system, and evaluates the idea that embryonic neu ral stem cel ls are heterogeneou s and restr icted. Stud ies that in dicate broad plasticity of adult The development of neural stem cells Sally Temple Center for Neuropharmaco logy and N euros cienc e, Albany Medica l Colleg e, 47 New Scotland Avenu e, Albany, New Yo rk 12208, USA (e-m ail: temples@ mail.amc.e du) The discovery of stem cells that can generate neural tissue has raised new possibilities for repairing the nervous system. A rush of papers proclaiming adult stem cell plasticity has fostered the notion that there is essentially one stem cell type that, with the right impetus, can create whatever progeny our heart, liver or other vital organ desires. But studies aimed at understanding the role of stem cells during development have led to a different view — that stem cells are restr icted regionally and temporally, and thus no t all stem cells are equivalent. Can these views be reconciled? insight review articles A–P axis Retinoids b a Shh D D V Cerebral cortex Basal forebrain Hippocampus Cerebellum (ref. 65) Spinal cord Neural crest (PNS) Embryo Adult Olfactory bulbs (ref. 63) Hippocampus Spinal cord Retina (ref. 64) SV Z Nasal epithelium (PNS) BMP BMP FGF Noggin Noggin Figure 1 The location of neural stem cells. a, The principal regions of the embr yonic and adult nervous system from which neural st em cells have been isolated 9,10,63–65 . b, Three models describing stem cells in the vertebrate neural plate. All neural plate cell s are stem cells (left), or stem cell s are a minor population that is evenly distribut ed (middle) or located in particular regions such as the midline and lateral edges (right). Factors such as bone morphogenetic prot eins (BMPs), Noggin, retinoids, Sonic hedgehog and fibroblast growth f actors (FG Fs) , w hich pr ovide anterior–posterior (A–P ) and dorsal–ventral (D–V ) patterning inf ormation, may regionalize stem cells 24 . © 2001 Macmillan Magazines Ltd

Development of NSCs

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