Deguchi Kimiko, Inoue Ken, Avila William E, Lopez-Terrada Dolores, Antalffy Barbara A, Quattrocchi Carlo C, Sheldon Michael, Mikoshiba Katsuhiko, D'Arcangelo Gabriella, Armstrong Dawna L
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
J Neuropathol Exp Neurol. 2003 Jun;62(6):676-84. doi: 10.1093/jnen/62.6.676.
In developing mammalian (mouse) brain, Reelin (Reln) is secreted by the Cajal-Retzius (CR) neurons in the marginal zone, binds apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (Vldlr), and induces the phosphorylation of the downstream cytoplasmic molecule disabled-1 (Dab1) in cortical plate neurons. Although this is a well-characterized signaling pathway in mice, it has not been well defined in human brain. In this paper we examined the expression of RELN, APOER2, VLDLR, and DAB1 in the developing human brain by RT-PCR. We further determined the cellular expression of the proteins RELN and DAB1 in 50 human brains ranging in age from 10 gestational weeks (GW) to 62 years using immunochemistry. We found that the pattern of expression of RELN and DAB1 in the human brain isnot identical to that observed in the mouse brain. In particular, we report the novel finding that human DAB1and RELN are coexpressed in CR neurons during cortical development and in cortical pyramidal neurons after neuronal migration is complete. Thus, in the human brain, the whole RELN signaling pathway is present within selected populations of cortical neurons throughout life. We speculate that RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function.
在发育中的哺乳动物（小鼠）大脑中，Reelin（Reln）由边缘区的Cajal-Retzius（CR）神经元分泌，与载脂蛋白E受体2（ApoER2）和极低密度脂蛋白受体（Vldlr）结合，并诱导皮质板神经元中下游细胞质分子失活-1（Dab1）的磷酸化。尽管这在小鼠中是一个已被充分表征的信号通路，但在人类大脑中尚未得到很好的定义。在本文中，我们通过逆转录聚合酶链反应（RT-PCR）检测了发育中的人类大脑中RELN、APOER2、VLDLR和DAB1的表达。我们进一步使用免疫化学方法确定了50个人类大脑中RELN和DAB1蛋白的细胞表达情况，这些大脑的年龄范围从妊娠10周（GW）到62岁。我们发现人类大脑中RELN和DAB1的表达模式与在小鼠大脑中观察到的不同。特别是，我们报告了一个新发现，即在皮质发育过程中，人类DAB1和RELN在CR神经元中共表达，在神经元迁移完成后，它们在皮质锥体神经元中也共表达。因此，在人类大脑中，整个Reelin信号通路在整个生命过程中都存在于特定的皮质神经元群体中。我们推测这些神经元中RELN和DAB1的共表达对于正常的皮质发育和成熟功能都是必要的。
