平面细胞极性通路核心基因与神经管畸形的相关性

Association between core genes in planar cell polarity pathway and neural tube defects

对平面细胞极性(planar cell polarity,PCP)信号通路中6种核心蛋白质(Frizzled、Flamingo、Vangl、Dishevelled、Prickle及Diego)的基本结构、在神经管畸形发生过程中的作用以及在人类神经管畸形患者中发现的相关突变位点的研究现状进行了综述.研究表明,接受Wnt信号通路刺激后这6个蛋白结合形成不对称性分布的膜复合物,经下游Rho/Rac信号通路来共同决定神经元的平面细胞极性及神经管的闭合.目前已在Frizzled、Vangl、Flamingo及Prickle 4个基因中发现了多个特异性错义突变,在Dishevelled基因中发现有SNP位点改变,Diego基因在神经管畸形中的突变不明.未来研究应在阐明核心基因与环境因素如何互作、核心基因SNP位点或突变如何影响其蛋白功能,从而参与神经管畸形发生方面进行突破.

The roles,the basic structure and the rare mutations in human neural tube defects（NTDs） were invesitaged of the six core proteins in the planar cell polarity（PCP） pathway（Frizzled,Flamingo,Vangl,Dishevelled,Prickle and Diego）.It has been revealed that upon stimulation from Wnt signaling pathway,these six proteins formed a membrane complex with asymmetric localization and determined the planar cell polarity of neuron cells via downstream Rho/Rac signaling pathway during neural tube closure.Up to now,several specific missense mutations have been identified in Frizzled,Vangl,Flamingo and Prickle genes,SNP site alterations have also been found in Dishevelled gene,but mutations in Diego gene is still unknown.In the future,great efforts should be made to elucidate how these core genes interact with environment factors in PCP pathway,and how SNP sites or mutation of core genes influence their protein functions which may then participate in neural tube defects.