title: Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo.
abstract: To identify the fates that astroglial cells can attain in the postnatal brain, we generated mice carrying an inducible Cre recombinase (Cre-ER(T2)) controlled by the human GFAP promoter (hGFAP). In mice carrying the GCE (hGFAP-Cre-ER(T2)) transgene, OHT (4-hydroxy-tamoxifen) injections induced Cre recombination in astroglial cells at postnatal day 5 and allowed us to permanently tag these cells with reporter genes. Three days after recombination, reporter-tagged cells were quiescent astroglial cells that expressed the stem cell marker LeX in the subventricular zone (SVZ) and dentate gyrus (DG). After 2-4 weeks, the tagged GFAP lineage included proliferating progenitors expressing the neuronal marker Dcx (Doublecortin) in the SVZ and the DG. After 4 weeks, the GFAP lineage generated mature neurons in the olfactory bulb (OB), DG, and, strikingly, also in the cerebral cortex. A major portion of all neurons in the DG and OB born at the end of the first postnatal week were generated from GFAP+ cells. In addition to neurons, mature oligodendrocytes and astrocytes populating the cerebral cortex and white matter were also the progeny of GFAP+ astroglial ancestors. Thus, genetic fate mapping of postnatal GFAP+ cells reveals that they seed the postnatal brain with neural progenitors/stem cells that in turn give rise to neural precursors and their mature neuronal and oligodendrocytic progeny in many CNS regions, including the cerebral cortex.
authors.affiliation: Child Study Center, Yale University Medical School, New Haven, Connecticut 06520, USA.
authors.forename: Yosif M
authors.initials: YM
authors.lastname: Ganat
authors.forename: John
authors.initials: J
authors.lastname: Silbereis
authors.forename: Clinton
authors.initials: C
authors.lastname: Cave
authors.forename: Hai
authors.initials: H
authors.lastname: Ngu
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ment
authors.forename: Flora M
authors.initials: FM
authors.lastname: Vaccarino
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002552:Cerebral Ventricles; D000089662:Doublecortin Protein; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006801:Humans; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D009830:Olfactory Bulb / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D013234:Stem Cells / Q000166:cytology*; D019076:Transgenes
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; C045073:Cre recombinase; D019426:Integrases