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Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of oligodendrocyte differentiation in the developing CNS
- Source :
- Development. 141:548-555
- Publication Year :
- 2014
- Publisher :
- The Company of Biologists, 2014.
-
Abstract
- In the central nervous system (CNS), oligodendrocyte maturation and axonal myelination occur on a predictable schedule, but the underlying timing mechanisms are largely unknown. In the present study, we demonstrate that Nkx2.2 homeodomain transcription factor is a key regulator for the timing of oligodendrocyte differentiation during development. Whereas induced expression of Nkx2.2 in early oligodendrocyte precursor cells (OPCs) causes precocious differentiation of oligodendrocytes, conditional ablation of Nkx2.2 temporally delays oligodendrocyte maturation. Moreover, Nkx2.2 can directly bind to the promoter of platelet-derived growth factor receptor alpha (Pdgfra) and repress its gene expression. Genetic ablation of Pdgfra mimics the effect of Nkx2.2 overexpression in accelerating OPC differentiation in the developing spinal cord. Together, our findings strongly suggest that Nkx2.2 functions as a major ‘switch’ to turn off Pdgfra signaling in OPCs and initiate the intrinsic program for oligodendrocyte differentiation.
- Subjects :
- Central Nervous System
Receptor, Platelet-Derived Growth Factor alpha
Time Factors
Cellular differentiation
Molecular Sequence Data
PDGFRA
Biology
Mice
Growth factor receptor
Cell Movement
medicine
Animals
Cell Lineage
Promoter Regions, Genetic
Molecular Biology
Transcription factor
Myelin Sheath
Cell Proliferation
Homeodomain Proteins
Genetics
Base Sequence
Stem Cells
Oligodendrocyte differentiation
Gene Expression Regulation, Developmental
Cell Differentiation
Zebrafish Proteins
Stem Cells and Regeneration
Oligodendrocyte
Cell biology
Oligodendroglia
Homeobox Protein Nkx-2.2
Phenotype
medicine.anatomical_structure
Mutation
embryonic structures
Homeobox
Stem cell
Protein Binding
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....a512effbae3d8695dd95137aa483c166