Andrade Nuno, Komnenovic Vukoslav, Blake Sophia M, Jossin Yves, Howell Brian, Goffinet Andre, Schneider Wolfgang J, Nimpf Johannes
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria.
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8508-13. doi: 10.1073/pnas.0611391104. Epub 2007 May 9.
Postnatal migration of interneuron precursors from the subventricular zone to the olfactory bulb occurs in chains that form the substrate for the rostral migratory stream. Reelin is suggested to induce detachment of neuroblasts from the chains when they arrive at the olfactory bulb. Here we show that ApoER2 and possibly very-low-density lipoprotein receptor (VLDLR) and their intracellular adapter protein Dab1 are involved in chain formation most likely independent of Reelin. F-spondin, which is present in the stream, may act as ligand for ApoER2 and VLDLR. In mice lacking either both receptors or Dab1 chain formation is severely compromised, and as a consequence the rostral migratory stream is virtually absent and neuroblasts accumulate in the subventricular zone. The mutant animals exhibit severe neuroanatomical defects in the subventricular zone and in the olfactory bulb. These data demonstrate a cell-autonomous function of ApoER2, and most likely VLDLR and Dab1, in postnatal migration of neuroblasts in the forebrain, which is suggested to depend on ligands other than Reelin.
中间神经元前体细胞从脑室下区向嗅球的产后迁移以链状形式发生，这些链构成了嘴侧迁移流的基质。据推测，当神经母细胞到达嗅球时，Reelin会诱导它们从链上脱离。在这里我们表明，载脂蛋白E受体2（ApoER2）以及可能的极低密度脂蛋白受体（VLDLR）及其细胞内衔接蛋白Dab1参与链的形成，这很可能独立于Reelin。存在于迁移流中的F-spondin可能作为ApoER2和VLDLR的配体。在缺乏这两种受体或Dab1的小鼠中，链的形成严重受损，结果嘴侧迁移流几乎不存在，神经母细胞在脑室下区积聚。突变动物在脑室下区和嗅球表现出严重的神经解剖学缺陷。这些数据证明了ApoER2以及很可能还有VLDLR和Dab1在前脑产后神经母细胞迁移中的细胞自主功能，这一功能被认为依赖于Reelin以外的配体。
