GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain.
Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.
Garcia
A Denise R
AD
Department of Neurobiology and Brain Research Institute, University of California, Los Angeles, California 90095-1763, USA.
Doan
Ngan B
NB
Imura
Tetsuya
T
Bush
Toby G
TG
Sofroniew
Michael V
MV
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048429:Cell Size; D000089622:Doublecortin Domain Proteins; D015774:Ganciclovir / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics; D014404:Tubulin / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D039842:Neural Cell Adhesion Molecule L1; D009479:Neuropeptides; D012794:Sialic Acids; D014404:Tubulin; C462941:beta3 tubulin, mouse; C103469:polysialyl neural cell adhesion molecule; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D015774:Ganciclovir