Sox9 and Sox10 influence survival and migration of oligodendrocyte precursors in the spinal cord by regulating PDGF receptor α expression
2008
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 α expression in the mutant
oligodendrocyte precursors, arguing that PDGF receptor α is under
transcriptional control of Sox9 and Sox10. Altered PDGF receptor α
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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