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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation
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Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation

机译：RhoA在神经祖细胞中的丢失导致粘附连接的破坏和过度增殖

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摘要

The organization of neural progenitors in the developing mammalian neuroepithelium is marked by cadherin-based adherens junctions. Whereas RhoA, a founding member of the small Rho GTPase family, has been shown to play important roles in epithelial adherens junctions, its physiological roles in neural development remain uncertain due to the lack of specific loss-of-function studies. Here, we show that RhoA protein accumulates at adherens junctions in the developing mouse brain and colocalizes to the cad-herin-catenin complex. Conditional deletion of RhoA in midbrain and forebrain neural progenitors using Wnt1-Cre and Foxgi-Cre mice, respectively, disrupts apical adherens junctions and causes massive dysplasia of the brain. Furthermore, RhoA-deiicient neural progenitor cells exhibit accelerated proliferation, reduction of cell-cycle exit and increased expression of downstream target genes of the hedgehog pathway. Consequently, both lines of conditional RhoA-deficient embryos exhibit expansion of neural progenitor cells and exencephaly-like protrusions. These results demonstrate a critical role of RhoA in the maintenance of apical adherens junctions and the regulation of neural progenitor proliferation in the developing mammalian brain.
机译：在发展中的哺乳动物神经上皮细胞中神经祖细胞的组织以基于钙粘着蛋白的粘附连接为标志。 RhoA是小的Rho GTPase家族的创始成员，尽管在上皮黏附连接中起着重要作用，但由于缺乏具体的功能丧失研究，其在神经发育中的生理作用仍然不确定。在这里，我们显示RhoA蛋白积聚在发育中的小鼠大脑的粘附连接处，并共定位于cad-herin-catenin复合物。分别使用Wnt1-Cre和Foxgi-Cre小鼠有条件地删除中脑和前脑神经祖细胞中的RhoA，会破坏根尖黏附连接并导致大脑大量发育异常。此外，RhoA样神经祖细胞表现出加速的增殖，细胞周期退出的减少和刺猬通路的下游目标基因的表达增加。因此，这两个条件性RhoA缺陷型胚胎都表现出神经祖细胞的扩展和脑电图样突起。这些结果证明了RhoA在维持发展中的哺乳动物脑中的根尖粘附连接和调节神经祖细胞增殖中的关键作用。

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  • 作者

    Kei-ichi Katayama; Jaime Melendez; Jessica M. Baumann; Jennifer R. Leslie; Bharesh K. Chauhan; Niza Nemkul; Richard A. Lang; Chia-Yi Kuan; Yi Zheng; Yutaka Yoshida;

  • 作者单位

    Developmental Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Developmental Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Developmental Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Ophthalmology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Developmental Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Ophthalmology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Developmental Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

    Developmental Biology, Cincinnati Children's Hospital Medical Center,Cincinnati, OH 45229;

  • 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

    cns development; cell adhesion;

    机译：cns发育;细胞粘附;

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