SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function.
The myelin-forming oligodendrocytes are an excellent model to study transcriptional regulation of specification events, lineage progression, and terminal differentiation in the central nervous system. Here, we show that the group D Sox transcription factors Sox5 and Sox6 jointly and cell-autonomously regulate several stages of oligodendrocyte development in the mouse spinal cord. They repress specification and terminal differentiation and influence migration patterns. As a consequence, oligodendrocyte precursors and terminally differentiating oligodendrocytes appear precociously in spinal cords deficient for both Sox proteins. Sox5 and Sox6 have opposite functions than the group E Sox proteins Sox9 and Sox10, which promote oligodendrocyte specification and terminal differentiation. Both genetic as well as molecular evidence suggests that Sox5 and Sox6 directly interfere with the function of group E Sox proteins. Our studies reveal a complex regulatory network between different groups of Sox proteins that is essential for proper progression of oligodendrocyte development.
Stolt
C Claus
CC
Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, D-91054 Erlangen, Germany.
Schlierf
Anita
A
Lommes
Petra
P
Hillgärtner
Simone
S
Werner
Torsten
T
Kosian
Thomas
T
Sock
Elisabeth
E
Kessaris
Nicoletta
N
Richardson
William D
WD
Lefebvre
Veronique
V
Wegner
Michael
M
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; D055757:SOXE Transcription Factors; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; C089186:Sox5 protein, mouse; C095939:Sox6 protein, mouse; C527933:Sox9 protein, mouse; D014157:Transcription Factors