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Sox2 and Pax6 maintain the proliferative and developmental potential of gliogenic neural stem cells In vitro.

TitleSox2 and Pax6 maintain the proliferative and developmental potential of gliogenic neural stem cells In vitro.
Publication TypeJournal Article
Year of Publication2011
AuthorsGómez-López S, Wiskow O, Favaro R, Nicolis SK, Pollard SM, Smith A
Date Published2011 Nov
KeywordsAnimals, Astrocytes, Blotting, Western, Cell Proliferation, Cells, Cultured, Colony-Forming Units Assay, Eye Proteins, Fatty Acid-Binding Proteins, Flow Cytometry, Gene Dosage, Homeodomain Proteins, Immunohistochemistry, Intermediate Filament Proteins, Mice, Mice, Knockout, Nerve Tissue Proteins, Nestin, Neural Stem Cells, Neuroglia, Oligodendroglia, Paired Box Transcription Factors, Real-Time Polymerase Chain Reaction, Repressor Proteins, SOXB1 Transcription Factors

Radial-glia-like neural stem (NS) cells may be derived from neural tissues or via differentiation of pluripotent embryonic stem (ES) cells. However, the mechanisms controlling NS cell propagation and differentiation are not yet fully understood. Here we investigated the roles of Sox2 and Pax6, transcription factors widely expressed in central nervous system (CNS) progenitors, in mouse NS cells. Conditional deletion of either Sox2 or Pax6 in forebrain-derived NS cells reduced their clonogenicity in a gene dosage-dependent manner. Cells heterozygous for either gene displayed moderate proliferative defects, which may relate to human pathologies attributed to SOX2 or PAX6 deficiencies. In the complete absence of Sox2, cells exited the cell cycle with concomitant downregulation of neural progenitor markers Nestin and Blbp. This occurred despite expression of the close relative Sox3. Ablation of Pax6 also caused major proliferative defects. However, a subpopulation of cells was able to expand continuously without Pax6. These Pax6-null cells retained progenitor markers but had altered morphology. They exhibited compromised differentiation into astrocytes and oligodendrocytes, highlighting that the role of Pax6 extends beyond neurogenic competence. Overall these findings indicate that Sox2 and Pax6 are both critical for self-renewal of differentiation-competent radial glia-like NS cells.

Alternate JournalGlia
PubMed ID21766338
Grant ListG0800784 / / Medical Research Council / United Kingdom
G1100526 / / Medical Research Council / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
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