Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes.
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, most of which differentiate into neurons, with a small subpopulation 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 the striatum, septum, corpus callosum, and fimbria-fornix. Most of these B1-derived cells gave rise to cells in the oligodendrocyte lineage, including local NG2+ progenitors, and pre-myelinating and myelinating oligodendrocytes. SVZ B1 cells also gave rise to a population of highly-branched S100beta+/glial fibrillary acidic protein (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, an 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.
Gonzalez-Perez
Oscar
O
Department of Neurological Surgery, Brain Tumor Research Center, Institute for Regeneration Medicine, University of California, San Francisco, California, USA.
Romero-Rodriguez
Ricardo
R
Soriano-Navarro
Mario
M
Garcia-Verdugo
Jose Manuel
JM
Alvarez-Buylla
Arturo
A
D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000166:cytology* / Q000378:metabolism; D003711:Demyelinating Diseases; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D004815:Epidermal Growth Factor