Förster Eckart, Tielsch Albrecht, Saum Barbara, Weiss Karl Heinz, Johanssen Celine, Graus-Porta Diana, Müller Ulrich, Frotscher Michael
Anatomisches Institut, Universität Freiburg, P.O. Box 111, D-79001 Freiburg, Germany.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13178-83. doi: 10.1073/pnas.202035899. Epub 2002 Sep 20.
The extracellular matrix molecule Reelin is required for the correct positioning of neurons during the development of the forebrain. However, the mechanism of Reelin action on neuronal migration is poorly understood. Reelin is assumed to act on neurons directly, but it may also affect the differentiation of glial cells necessary for neuronal migration. Here we show that a regular glial scaffold fails to form in vivo in the dentate gyrus of mice deficient of Reelin or Disabled 1, a neuronal adaptor protein in the Reelin signaling pathway. A subset of these defects is observed in mice that lack beta(1)-class integrins, known to bind Reelin. Moreover, recombinant Reelin induced branching of glial processes in vitro. Our data suggest that Reelin affects glial differentiation via Disabled 1 and beta(1)-class integrin-dependent signaling pathways.
细胞外基质分子Reelin在前脑发育过程中对于神经元的正确定位是必需的。然而,Reelin对神经元迁移的作用机制仍知之甚少。一般认为Reelin直接作用于神经元,但它也可能影响神经元迁移所必需的神经胶质细胞的分化。在这里我们表明,在缺乏Reelin或Disabled 1(Reelin信号通路中的一种神经元衔接蛋白)的小鼠齿状回中,体内无法形成正常的神经胶质支架。在缺乏已知可结合Reelin的β(1)类整合素的小鼠中也观察到了这些缺陷的一部分。此外,重组Reelin在体外诱导了神经胶质细胞突起的分支。我们的数据表明,Reelin通过Disabled 1和β(1)类整合素依赖性信号通路影响神经胶质细胞的分化。