Monk Kelly R, Naylor Stephen G, Glenn Thomas D, Mercurio Sara, Perlin Julie R, Dominguez Claudia, Moens Cecilia B, Talbot William S
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science. 2009 Sep 11;325(5946):1402-5. doi: 10.1126/science.1173474.
The myelin sheath allows axons to conduct action potentials rapidly in the vertebrate nervous system. Axonal signals activate expression of specific transcription factors, including Oct6 and Krox20, that initiate myelination in Schwann cells. Elevation of cyclic adenosine monophosphate (cAMP) can mimic axonal contact in vitro, but the mechanisms that regulate cAMP levels in vivo are unknown. Using mutational analysis in zebrafish, we found that the G protein-coupled receptor Gpr126 is required autonomously in Schwann cells for myelination. In gpr126 mutants, Schwann cells failed to express oct6 and krox20 and were arrested at the promyelinating stage. Elevation of cAMP in gpr126 mutants, but not krox20 mutants, could restore myelination. We propose that Gpr126 drives the differentiation of promyelinating Schwann cells by elevating cAMP levels, thereby triggering Oct6 expression and myelination.
髓鞘使轴突能够在脊椎动物神经系统中快速传导动作电位。轴突信号激活特定转录因子的表达，包括Oct6和Krox20，这些转录因子启动施万细胞的髓鞘形成。环磷酸腺苷（cAMP）水平升高在体外可模拟轴突接触，但体内调节cAMP水平的机制尚不清楚。通过对斑马鱼进行突变分析，我们发现G蛋白偶联受体Gpr126在施万细胞中自主发挥作用，是髓鞘形成所必需的。在gpr126突变体中，施万细胞无法表达oct6和krox20，并停滞在前髓鞘形成阶段。gpr126突变体而非krox20突变体中cAMP水平的升高可恢复髓鞘形成。我们提出，Gpr126通过提高cAMP水平驱动前髓鞘形成施万细胞的分化，从而触发Oct6表达和髓鞘形成。
