Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
Exp Neurol. 2012 Aug;236(2):259-67. doi: 10.1016/j.expneurol.2012.04.012. Epub 2012 Apr 24.
Cell migration is an indispensable aspect of tissue patterning during embryonic development. Oligodendrocytes, the myelinating cells of the central nervous system, migrate significantly during development of the brain. Several growth factors have been identified as being critical regulators of oligodendrocyte progenitor migration, including platelet derived growth factor-A (PDGFA), and fibroblast growth factor-2 (FGF2). Further, the chemokine CXCL1 has been shown to play a critical role in regulating the dispersal of oligodendrocyte progenitors during development, although the mechanisms underlying this regulation are unknown. Previous studies have also shown that calcium flux is required for oligodendrocyte progenitor migration. CXCL1 induces calcium flux in cells; therefore, we hypothesized that CXCL1 inhibition of oligodendrocyte progenitor migration is regulated via changes in intracellular calcium flux. The current study shows that CXCL1 inhibition of oligodendrocyte progenitor migration is independent of calcium signaling. Further, we show that CXCL1 inhibition of oligodendrocyte progenitor migration is specific to PDGFA induced migration. Finally, we show that CXCL1 inhibition of oligodendrocyte progenitor migration is independent of activation of the cell cycle. Our results provide intriguing results relevant to specific aspects of patterning of white matter tracts in the central nervous system, and may further the understanding of tissue remodeling seen during disease-related processes.
细胞迁移是胚胎发育过程中组织模式形成不可或缺的一个方面。少突胶质细胞是中枢神经系统的髓鞘形成细胞，在大脑发育过程中会发生显著迁移。已经确定了几种生长因子作为少突胶质前体细胞迁移的关键调节因子，包括血小板衍生生长因子-A（PDGFA）和成纤维细胞生长因子-2（FGF2）。此外，趋化因子 CXCL1 已被证明在调节少突胶质前体细胞在发育过程中的分散中发挥关键作用，尽管这种调节的机制尚不清楚。先前的研究还表明，钙通量对于少突胶质前体细胞的迁移是必需的。CXCL1 诱导细胞中的钙通量；因此，我们假设 CXCL1 抑制少突胶质前体细胞的迁移是通过细胞内钙通量的变化来调节的。本研究表明，CXCL1 抑制少突胶质前体细胞的迁移与钙信号无关。此外，我们表明，CXCL1 抑制少突胶质前体细胞的迁移是 PDGFA 诱导的迁移所特有的。最后，我们表明，CXCL1 抑制少突胶质前体细胞的迁移与细胞周期的激活无关。我们的结果提供了与中枢神经系统白质束形成的特定方面相关的有趣结果，并可能进一步了解疾病相关过程中观察到的组织重塑。
