ApoER2/VLDL receptor and Dab1 in the rostral migratory stream function in postnatal neuronal migration independently of Reelin
ApoER2/VLDL receptor and Dab1 in the rostral migratory stream function in postnatal neuronal migration independently of Reelin
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DOI：
10.1073/pnas.0611391104
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发表时间：
2007-05-15
影响因子：
11.1
通讯作者：
Nimpf, Johannes
中科院分区：
文献类型：
--
作者：
Andrade, Nuno;Komnenovic, Vukoslav;Nimpf, Johannes
出生后中间神经元前体从室下区到嗅球的迁移发生在形成吻端迁移流基质的链中。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 ApoER2 和可能的极低密度脂蛋白受体 (VLDLR) 及其细胞内衔接蛋白 Dab1 参与链形成，很可能独立于 Reelin。存在于流中的 F-spondin 可能充当 ApoER2 和 VLDLR 的配体。在缺乏这两种受体或Dab1链形成的小鼠中，头侧迁移流实际上不存在，神经母细胞在脑室下区积聚。突变动物的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 以及最有可能的 VLDLR 和 Dab1 在前脑神经母细胞出生后迁移中的细胞自主功能，这被认为依赖于 Reelin 以外的配体。
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.