FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells.
The embryonic cerebral cortex contains a population of stem-like founder cells capable of generating large, mixed clones of neurons and glia in vitro. We report that the default state of early cortical stem cells is neuronal, and that stem cells are heterogeneous in the number of neurons that they generate. In low fibroblast growth factor (FGF2) concentrations, most maintain this specification, generating solely neuronal progeny. Oligodendroglial production within these clones is stimulated by a higher, threshold level of FGF2, and astrocyte production requires additional environmental factors. Because most cortical neurons are born before glia in vivo, these data support a model in which the scheduled production of cortical cells involves an intrinsic neuronal program in the early stem cells and exposure to environmental, glia-inducing signals.
Qian
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Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208, USA.
Davis
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AA
Goderie
S K
SK
Temple
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S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D002999:Clone Cells; D017931:DNA Primers; D005314:Embryonic and Fetal Development; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D051379:Mice; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2