Feigenson Keith, Reid Mary, See Jill, Crenshaw E Bryan, Grinspan Judith B
Department of Research Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mol Cell Neurosci. 2009 Nov;42(3):255-65. doi: 10.1016/j.mcn.2009.07.010. Epub 2009 Jul 18.
The development of oligodendrocytes, the myelinating cells of the central nervous system, is temporally and spatially controlled by local signaling factors acting as inducers or inhibitors. Dorsal spinal cord tissue has been shown to contain inhibitors of oligodendrogliogenesis, although their identity is not completely known. We have studied the actions of one family of dorsal signaling molecules, the Wnts, on oligodendrocyte development. Using tissue culture models, we have shown that canonical Wnt activity through beta-catenin activation inhibits oligodendrocyte maturation, independently of precursor proliferation, cell death, or diversion to an alternate cell fate. Mice in which Wnt/beta-catenin signaling was constitutively activated in cells of the oligodendrocyte lineage had equal numbers of oligodendrocyte precursors relative to control littermates, but delayed appearance of mature oligodendrocytes, myelin protein, and myelinated axons during development, although these differences largely disappeared by adulthood. These results indicate that activating the Wnt/beta-catenin pathway delays the development of myelinating oligodendrocytes.
少突胶质细胞是中枢神经系统的髓鞘形成细胞，其发育受到作为诱导剂或抑制剂的局部信号因子在时间和空间上的控制。尽管背侧脊髓组织中少突胶质细胞生成抑制剂的具体身份尚不完全清楚，但已证明其含有此类抑制剂。我们研究了一类背侧信号分子——Wnt蛋白对少突胶质细胞发育的作用。利用组织培养模型，我们发现通过β-连环蛋白激活的经典Wnt活性可抑制少突胶质细胞成熟，这一过程与前体细胞增殖、细胞死亡或细胞命运转向无关。在少突胶质细胞谱系细胞中组成性激活Wnt/β-连环蛋白信号的小鼠，相对于对照同窝小鼠，少突胶质细胞前体细胞数量相等，但在发育过程中成熟少突胶质细胞、髓鞘蛋白和有髓轴突的出现延迟，不过这些差异在成年后基本消失。这些结果表明，激活Wnt/β-连环蛋白信号通路会延迟有髓少突胶质细胞的发育。
