EGF induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes

• Published in: Stem cells (Dayton, Ohio) Vol. 27; no. 8; pp. 2032 - 2043
• Main Authors: Gonzalez-Perez, Oscar, Romero-Rodriguez, Ricardo, Soriano-Navarro, Mario, Garcia-Verdugo, Jose Manuel, Alvarez-Buylla, Arturo
• Format: Journal Article
• Language: English
• Published: 01.08.2009
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.119

New neurons and oligodendrocytes are continuously produced in the subventricular zone ( SVZ ) of adult mammalian brains. Under normal conditions, the SVZ primary precursors (type B1 cells) generate type C cells, the majority of which differentiate into neurons, with a small sub-population giving rise to oligodendrocytes. Epidermal growth factor ( EGF ) signaling induces dramatic proliferation and migration of SVZ progenitors, a process that could have therapeutic applications. However, the fate of cells derived from adult neural stem cells after EGF stimulation remains unknown. Here, we specifically labeled SVZ B1 cells and followed their progeny after a 7-day intraventricular infusion of EGF. Cells derived from SVZ B1 cells invaded the parenchyma around the SVZ into striatum, septum, corpus callosum, and fimbria-fornix. The majority of these B1-derived cells gave rise to cells in the oligodendrocyte lineage including local NG2+ progenitors, pre-myelinating and myelinating oligodendrocytes. SVZ B1 cells also gave rise to a population of highly branched S100β+/GFAP+ cells in the striatum and septum, but no neuronal differentiation was observed. Interestingly, when demyelination was induced in the corpus callosum by a local injection of lysolecithin, increased number of cells derived from SVZ B1 cells and stimulated to migrate and proliferate by EGF infusion, differentiated into oligodendrocytes at the lesion site. This work indicates that EGF infusion can greatly expand the number of progenitors derived from the SVZ primary progenitors, which migrate and differentiate into oligodendroglial cells. This expanded population could be used for the repair of white matter lesions.