Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus.

Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus.
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DOI:
10.3389/fnins.2014.00418
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发表时间:
2014
影响因子:
4.3
通讯作者:
Badea A
Badea A
中科院分区:
医学2区
文献类型:
--
作者:
Ashbrook DG;Delprato A;Grellmann C;Klein M;Wetzel R;Overall RW;Badea A

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成人神经发生,即成人大脑中新神经元的终身产生,受到复杂的遗传控制,但许多相关基因仍有待确定。在这项研究中,我们已经整合了公开的基因表达数据从BXD和CXB重组近交系小鼠发现基因共表达的成年海马与巢蛋白,神经前体细胞群的共同标志物。此外,我们纳入了空间表达信息,以限制候选基因的高差异表达的海马齿状回的基因。从精选的蛋白质-蛋白质相互作用数据库中获得的数据揭示了我们的候选基因与那些已知参与成人神经发生的基因之间的相互作用。富集分析表明与Wnt/β-catenin通路有关,已知该通路参与成人神经发生。特别是,我们的候选人富含Lef 1的靶点,Lef 1是Wnt通路的调节剂。总之,我们结合生物信息学方法确定了6个参与成人神经发生的新候选基因:Amer 3,Eya 3,Mtdh,Nr 4a 3,Polr 2a和Tbkbp 1。此外,我们提出了一个作用,Lef 1转录控制成人海马前体细胞增殖的调节。
Adult neurogenesis, the lifelong production of new neurons in the adult brain, is under complex genetic control but many of the genes involved remain to be identified. In this study, we have integrated publicly available gene expression data from the BXD and CXB recombinant inbred mouse lines to discover genes co-expressed in the adult hippocampus with Nestin, a common marker of the neural precursor cell population. In addition, we incorporated spatial expression information to restrict candidates to genes with high differential gene expression in the hippocampal dentate gyrus. Incorporating data from curated protein-protein interaction databases revealed interactions between our candidate genes and those already known to be involved in adult neurogenesis. Enrichment analysis suggested a link to the Wnt/β-catenin pathway, known to be involved in adult neurogenesis. In particular, our candidates were enriched in targets of Lef1, a modulator of the Wnt pathway. In conclusion, our combination of bioinformatics approaches identified six novel candidate genes involved in adult neurogenesis; Amer3, Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. Further, we propose a role for Lef1 transcriptional control in the regulation of adult hippocampal precursor cell proliferation.
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