Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Wellcome Trust-MRC Stem Cell Institute, Cambridge Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, UK.
Nat Neurosci. 2017 Jan;20(1):10-15. doi: 10.1038/nn.4425. Epub 2016 Oct 24.
The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers. Thus, a neuronal program dependent on the phosphoinositide PI(3,4,5)P is sufficient to trigger all steps of myelination.
中枢神经系统髓鞘形成的分子触发因素尚不清楚。通过靶向小脑颗粒细胞中的 Pten 并激活 AKT1-mTOR 通路，我们增加了正常未髓鞘化轴突的口径和许多编码调节蛋白的基因的表达。这导致遗传上野生型少突胶质细胞前体细胞的扩增、少突胶质细胞分化和新的平行纤维髓鞘形成。因此，依赖于磷酸肌醇 PI(3,4,5)P 的神经元程序足以触发髓鞘形成的所有步骤。
