Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of oligodendrocyte differentiation in the developing CNS
Zhu Q, Zhao X, Zheng K, Li H, Huang H, Zhang Z, Mastracci T, Wegner M, Chen Y, Sussel L, Qiu M (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: Company of Biologists
Book Volume: 141
Pages Range: 548-55
Journal Issue: 3
DOI: 10.1242/dev.095323
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.
Authors with CRIS profile
Involved external institutions
University of Louisville (UofL)
United States (USA) (US)
Hangzhou Normal University / 杭州师范大学
China (CN)
Columbia University
United States (USA) (US)
Tulane University
United States (USA) (US)
United States (USA) (US)
Hangzhou Normal University / 杭州师范大学
China (CN)
Columbia University
United States (USA) (US)
Tulane University
United States (USA) (US)
How to cite
APA:
Zhu, Q., Zhao, X., Zheng, K., Li, H., Huang, H., Zhang, Z.,... Qiu, M. (2014). Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of oligodendrocyte differentiation in the developing CNS. Development, 141(3), 548-55. https://dx.doi.org/10.1242/dev.095323
MLA:
Zhu, Qiang, et al. "Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of oligodendrocyte differentiation in the developing CNS." Development 141.3 (2014): 548-55.
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