Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo

J Neurosci. 2006 Aug 16;26(33):8609-21. doi: 10.1523/JNEUROSCI.2532-06.2006.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / metabolism
  • Animals, Newborn / physiology*
  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Brain / cytology
  • Cell Differentiation*
  • Cell Lineage*
  • Cerebral Ventricles
  • Doublecortin Protein
  • Female
  • Glial Fibrillary Acidic Protein / genetics
  • Humans
  • Integrases / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / cytology*
  • Olfactory Bulb / cytology
  • Oligodendroglia / cytology
  • Promoter Regions, Genetic
  • Recombination, Genetic
  • Stem Cells / cytology*
  • Transgenes

Substances

  • Dcx protein, mouse
  • Doublecortin Protein
  • Glial Fibrillary Acidic Protein
  • Cre recombinase
  • Integrases