Niu Sanyong, Yabut Odessa, D'Arcangelo Gabriella
The Cain Foundation Laboratories, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurosci. 2008 Oct 8;28(41):10339-48. doi: 10.1523/JNEUROSCI.1917-08.2008.
The development of distinct cellular layers and precise synaptic circuits is essential for the formation of well functioning cortical structures in the mammalian brain. The extracellular protein Reelin, through the activation of a core signaling pathway, including the receptors ApoER2 and VLDLR (very low density lipoprotein receptor) and the adapter protein Dab1 (Disabled-1), controls the positioning of radially migrating principal neurons, promotes the extension of dendritic processes in immature forebrain neurons, and affects synaptic transmission. Here we report for the first time that the Reelin signaling pathway promotes the development of postsynaptic structures such as dendritic spines in hippocampal pyramidal neurons. Our data underscore the importance of Reelin as a factor that promotes the maturation of target neuronal populations and the development of excitatory circuits in the postnatal hippocampus. These findings may have implications for understanding the origin of cognitive disorders associated with Reelin deficiency.
不同细胞层和精确突触回路的发育对于哺乳动物大脑中功能良好的皮质结构的形成至关重要。细胞外蛋白Reelin通过激活包括受体ApoER2和极低密度脂蛋白受体(VLDLR)以及衔接蛋白Dab1(Disabled-1)在内的核心信号通路,控制放射状迁移的主神经元的定位,促进未成熟前脑神经元树突的延伸,并影响突触传递。在此,我们首次报告Reelin信号通路促进海马锥体神经元中树突棘等突触后结构的发育。我们的数据强调了Reelin作为促进产后海马中靶神经元群体成熟和兴奋性回路发育的一个因素的重要性。这些发现可能对理解与Reelin缺乏相关的认知障碍的起源具有启示意义。