title: Sox9 and Sox10 influence survival and migration of oligodendrocyte precursors in the spinal cord by regulating PDGF receptor alpha expression.
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.
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Fahrstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Finzsch
authors.forename: C Claus
authors.initials: CC
authors.lastname: Stolt
authors.forename: Petra
authors.initials: P
authors.lastname: Lommes
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D054338:Cell Transdifferentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000172:deficiency / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D019426:Integrases; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; D014157:Transcription Factors; C512773:Olig2 protein, mouse; C527924:Sox10 protein, mouse; C527933:Sox9 protein, mouse; C045073:Cre recombinase