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

Citations Over TimeTop 10% of 2014 papers

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.

Related Papers

• → Olig1 Function Is Required for Oligodendrocyte Differentiation in the Mouse Brain(2015)120 cited
• → Extracellular and intracellular regulation of oligodendrocyte development: Roles of Sonic hedgehog and expression of E proteins(2002)54 cited
• → Co‐localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes(2009)97 cited
• → The oligodendrocyte lineage genes Olig1 and Olig2 in CNS development(2002)
• Transcriptional Mechanisms of Oligodendrocyte Development and Their Response to Hypoxia(2014)