Sox9 and Sox10 influence survival and migration of oligodendrocyte precursors in the spinal cord by regulating PDGF receptor αexpression

Abstract

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.

FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

“…Studies in the mouse spinal cord have shown that Sox9 controls the specification of both oligodendrocytes and astrocytes and subsequently, in combination with Sox10, promotes the further development of OLPs (Stolt et al, 2003;Finzsch et al, 2008). We have shown that in the zebrafish hindbrain, sox9a is necessary for the generation of both OLPs and GS-positive astroglia, supporting a phylogenetically conserved role.…”

“…One important player is the high mobility group (HMG) factor Sox9, which is necessary for the downregulation of neurogenesis and the specification of both oligodendrocytes and astrocytes in the mouse spinal cord (Stolt et al, 2003). Following the production of oligodendrocyte progenitors (OLPs), Sox9 acts in combination with Sox10 to control their survival and migration (Finzsch et al, 2008). In addition, recent studies have shown that gliogenesis in the vertebrate retina is also under the control of Sox9 (Poche et al, 2008;Yokoi et al, 2009).…”

Transforming Growth Factor β-Mediated Sox10 Suppression Controls Mesenchymal Progenitor Generation in Neural Crest Stem Cells

“…In particular, the TGFb1-induced switch in NC cell plasticity is reflected by a change in the Sox code from a Sox10-positive/Sox9-negative to a Sox10-negative/Sox9-positive state. Although Sox9 and Sox10 are often coexpressed and act equivalently in NC induction and other processes of neural development [34,35], they exhibit different expression patterns during NC lineage decisions and fulfill fundamentally distinct functions in the transition of NCSCs to mesenchymal progenitor cells. Sox9 expression is induced by TGFb signaling during limb chondrogenesis [36] and in NCSCs, as shown here.…”

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

“…The initial specification of the oligodendrocyte lineage is dependent on olig2 and this lineage is absent from olig2-null mice [17] . olig2 induces transcription factors that are required for the generation of mature, postmitotic oligodendrocytes, notably olig1, Sox-10, Nkx2.2, Nkx6.2, Ying Yang 1, and ZFP488 [18][19][20][21][22][23] . in counterbalance, transcription [24][25][26] .…”