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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice
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Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice

机译：在大脑发育过程中Kruppel样因子4的失调导致小鼠脑积水

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摘要

Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripo-tency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of sub-ventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that down-regulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.
机译：Kruppel样因子4（KLF4）参与胚胎干细胞的自我更新和体细胞重编程为多能性。然而，其在谱系定型干细胞中的作用仍然未知。在这里，我们显示KLF4在神经干细胞（NSCs）中表达并且在神经元分化过程中被下调。出乎意料的是，增强的KLF4表达降低了培养的NSC的自我更新，并抑制了转基因小鼠脑室下神经前体的增殖。 NSC和源自NSC的室管膜细胞中KLF4升高的小鼠表现出脑积水样特征，包括脑室增大，皮层变薄，a体发育不全和显着减少的连合下器官。这些特征伴随着GFAP表达的升高和星形胶质细胞肥大。对脑脊液流动至关重要的心室纤毛在突变小鼠中也被破坏。这些结果表明，KLF4的下调对于神经发育至关重要，其失调可能导致脑积水。

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  • 作者

    Song Qin; Menglu Liu; Wenze Niu; Chun-Li Zhang;

  • 作者单位

    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;

    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;

    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;

    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    ependymal cilia; neurogenesis;

    机译：室管膜纤毛神经发生;

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