Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.
J Neurosci. 2013 Sep 4;33(36):14558-66. doi: 10.1523/JNEUROSCI.2001-12.2013.
Glial cells that express the NG2 proteoglycan and the α receptor for PDGF (NG2 cells, polydendrocytes) make up the fifth major cell population that serves as oligodendrocyte progenitor cells in the postnatal CNS. Although recent studies have suggested differences in their proliferation and oligodendrocyte differentiation in gray and white matter, the mechanism underlying the observed differences has been unclear. Using organotypic slice cultures from the forebrain and cerebellum of early postnatal NG2creBAC:ZEG mice, we have compared basal and growth factor-induced proliferation of NG2 cells in gray and white matter. NG2 cells in white matter exhibited greater proliferative response to PDGF AA than those in gray matter. Heterotopic slice transplant and explant cultures suggested intrinsic mechanisms for the differential proliferative response of gray and white matter cells. Additionally, younger white matter NG2 cells showed a more robust proliferative response to PDGF. Basal and PDGF-induced proliferation of gray and white matter NG2 cells was largely dependent on Wnt/β-catenin and phosphatidylinositol 3-kinase acting through the mammalian target of rapamycin pathway and not through ERK. These data uncover a previously unrecognized divergence between gray and white matter NG2 cells in the developing brain in their proliferative response to PDGF.
表达 NG2 蛋白聚糖和 PDGFα受体的神经胶质细胞（NG2 细胞，多形胶细胞）构成了第五大细胞群体，作为出生后中枢神经系统中的少突胶质前体细胞。尽管最近的研究表明它们在灰质和白质中的增殖和少突胶质分化存在差异，但观察到的差异的机制尚不清楚。使用来自早期出生后 NG2creBAC：ZEG 小鼠的大脑前脑和小脑的器官型切片培养物，我们比较了灰质和白质中 NG2 细胞的基础和生长因子诱导的增殖。白质中的 NG2 细胞对 PDGF AA 的增殖反应大于灰质中的 NG2 细胞。异位切片移植和外植体培养表明灰质和白质细胞增殖反应差异的内在机制。此外，年轻的白质 NG2 细胞对 PDGF 的增殖反应更强烈。灰质和白质 NG2 细胞的基础和 PDGF 诱导的增殖在很大程度上依赖于 Wnt/β-连环蛋白和通过哺乳动物雷帕霉素靶蛋白途径而不是通过 ERK 发挥作用的磷脂酰肌醇 3-激酶。这些数据揭示了发育中大脑中灰质和白质 NG2 细胞在对 PDGF 的增殖反应方面以前未被认识到的差异。
