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The Journal of Neuroscience, August 16, 2006, 26(33):8609-8621; doi:10.1523/JNEUROSCI.2532-06.2006

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Development/Plasticity/Repair
Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem Cells In Vivo

Yosif M. Ganat,^1 * John Silbereis,^1 * Clinton Cave,¹ Hai Ngu,¹ George M. Anderson,¹ Yasushi Ohkubo,¹ Laura R. Ment,² and Flora M. Vaccarino^1,3

¹Child Study Center and ²Departments of Pediatrics and Neurology and ³Neurobiology, Yale University Medical School, New Haven, Connecticut 06520

Correspondence should be addressed to Flora M. Vaccarino, Child Study Center, 230 South Frontage Road, New Haven, CT 06520. Email: lora.vaccarino{at}yale.edu

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.

Key words: astrocyte; glial fibrillary acidic protein; Cre recombinase; lineage; neural stem cells; LeX

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Received Sept. 23, 2005; revised July 6, 2006; accepted July 7, 2006.

Correspondence should be addressed to Flora M. Vaccarino, Child Study Center, 230 South Frontage Road, New Haven, CT 06520. Email: lora.vaccarino{at}yale.edu

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