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The Journal of Neuroscience, July 26, 2006, 26(30):7907-7918; doi:10.1523/JNEUROSCI.1299-06.2006

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Development/Plasticity/Repair
Origin of Oligodendrocytes in the Subventricular Zone of the Adult Brain

Bénédicte Menn,¹ Jose Manuel Garcia-Verdugo,² Cynthia Yaschine,¹ Oscar Gonzalez-Perez,¹ David Rowitch,³ and Arturo Alvarez-Buylla¹

¹Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California at San Francisco, San Francisco, California 94143, ²University of Valencia, 46010 Valencia, Spain, and ³Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to Arturo Alvarez-Buylla, Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California at San Francisco, Box 0525, San Francisco, CA 94143. abuylla{at}stemcell.ucsf.edu

Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the subventricular zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs). Here we show that type B cells also generate a small number of nonmyelinating NG2-positive OPCs and mature myelinating oligodendrocytes. Some type B cells and a small subpopulation of actively dividing type C (transit-amplifying) cells expressed oligodendrocyte lineage transcription factor 2 (Olig2), suggesting that oligodendrocyte differentiation in the SVZ begins early in the lineage. Olig2-positive, polysialylated neural cell adhesion molecule-positive, PDGF receptor -positive, and -tubulin-negative cells originating in the SVZ migrated into corpus callosum, striatum, and fimbria fornix to differentiate into the NG2-positive nonmyelinating and mature myelinating oligodendrocytes. Furthermore, primary clonal cultures of type B cells gave rise to oligodendrocytes alone or oligodendrocytes and neurons. Importantly, the number of oligodendrocytes derived from type B cells in vivo increased fourfold after a demyelinating lesion in corpus callosum, indicating that SVZ astrocytes participate in myelin repair in the adult brain. Our work identifies SVZ type B cells as progenitors of oligodendrocytes in normal and injured adult brain.

Key words: adult oligodendrogenesis; CNS stem cells; oligodendrocyte progenitors; SVZ astrocyte; myelin repair; Olig2

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Received Oct. 24, 2005; revised June 19, 2006; accepted June 21, 2006.

Correspondence should be addressed to Arturo Alvarez-Buylla, Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California at San Francisco, Box 0525, San Francisco, CA 94143. abuylla{at}stemcell.ucsf.edu

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