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Publication : Sox9 and Sox10 influence survival and migration of oligodendrocyte precursors in the spinal cord by regulating PDGF receptor alpha expression.

First Author  Finzsch M Year  2008
Journal  Development Volume  135
Issue  4 Pages  637-46
PubMed ID  18184726 Mgi Jnum  J:130977
Mgi Id  MGI:3772617 Doi  10.1242/dev.010454
Citation  Finzsch M, et al. (2008) Sox9 and Sox10 influence survival and migration of oligodendrocyte precursors in the spinal cord by regulating PDGF receptor {alpha} expression. Development 135(4):637-46
abstractText  Specification of the myelin-forming oligodendrocytes of the central nervous system requires the Sox9 transcription factor, whereas terminal differentiation depends on the closely related Sox10. Between specification and terminal differentiation, Sox9 and Sox10 are co-expressed in oligodendrocyte precursors and are believed to exert additional functions. To identify such functions, we have deleted Sox9 specifically in already specified oligodendrocyte precursors of the spinal cord. In the absence of Sox9, oligodendrocyte precursors developed normally and started terminal differentiation on schedule. However, when Sox10 was additionally deleted, oligodendrocyte precursors exhibited an altered migration pattern and were present in reduced numbers because of increased apoptosis rates. Remaining precursors continued to express many characteristic oligodendroglial markers. Aberrant expression of astrocytic and neuronal markers was not observed. Strikingly, we failed to detect PDGF receptor alpha expression in the mutant oligodendrocyte precursors, arguing that PDGF receptor alpha is under transcriptional control of Sox9 and Sox10. Altered PDGF receptor alpha expression is furthermore sufficient to explain the observed phenotype, as PDGF is both an important survival factor and migratory cue for oligodendrocyte precursors. We thus conclude that Sox9 and Sox10 are required in a functionally redundant manner in oligodendrocyte precursors for PDGF-dependent survival and migration.
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