Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of oligodendrocyte differentiation in the developing CNS

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Zhu Q, Zhao X, Zheng K, Li H, Huang H, Zhang Z, Mastracci T, Wegner M, Chen Y, Sussel L, Qiu M
Zeitschrift: Development
Verlag: Company of Biologists
Jahr der Veröffentlichung: 2014
Band: 141
Heftnummer: 3
Seitenbereich: 548-55
ISSN: 0950-1991
eISSN: 1477-9129


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.


FAU-Autoren / FAU-Herausgeber

Wegner, Michael Prof. Dr.
Lehrstuhl für Biochemie und Pathobiochemie


Autor(en) der externen Einrichtung(en)
Columbia University
Hangzhou Normal University / 杭州师范大学
Tulane University
University of Louisville (UofL)


Zitierweisen

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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Zuletzt aktualisiert 2018-08-10 um 02:46