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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network
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Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network

机译:重复性AP2a活性控制神经c基因调控网络中的顺序步骤

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摘要

The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC emergence; however, the role of AP2 factors at the NB remains unclear. We show here that AP2a initiates NB patterning and is sufficient to elicit a NB-like pattern in neuralized ectoderm. In contrast, the other early regulators do not participate in ap2a initiation at the NB, but cooperate to further establish a robust NB pattern. The NC regulatory network uses a multistep cascade of secreted inducers and transcription factors, first at the NB and then within the NC progenitors. Here we report that AP2a acts at two distinct steps of this cascade. As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB and activate pax3; as a NC specifier, AP2a regulates further NC development independent of and downstream of NB patterning. Our findings reconcile conflicting observations from various vertebrate organisms. AP2a provides a paradigm for the reiterated use of multifunctional molecules, thereby facilitating emergence of the NC in vertebrates.
机译:神经波峰(NC)来自发生在其祖域神经边界(NB)内的组合感应事件。几个转录因子在NB早期起作用,但是起始分子事件仍然难以捉摸。来自基础脊椎动物的最新数据表明,ap2可能对NC的出现至关重要。但是,AP2因子在NB中的作用仍不清楚。我们在这里显示,AP2a启动了NB模式,并足以在神经化外胚层中引发NB样模式。相比之下,其他早期监管机构则不参与NB的ap2a启动,而是合作进一步建立稳健的NB模式。 NC调节网络首先在NB,然后在NC祖细胞内使用分泌的诱导物和转录因子的多级级联。在这里,我们报告AP2a在此级联的两个不同步骤中起作用。作为最早已知的NB指定者,AP2a介导Wnt信号以启动NB并激活pax3。作为NC指定者,AP2a可以独立于NB图案及其下游来调节NC的进一步发展。我们的发现调和了来自各种脊椎动物的相互矛盾的观察结果。 AP2a为重复使用多功能分子提供了范例,从而促进了NC在脊椎动物中的出现。

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  • 作者单位

    Institut Curie, Institut National de la Sante et de la Recherche Medicale U1021, Centre National de la Recherche Scientifique Unite Mixte de Recherche 3347,F-91405 Orsay, France,Universite Paris Sud-11, F-91405 Orsay, France;

    Institut Curie, Institut National de la Sante et de la Recherche Medicale U1021, Centre National de la Recherche Scientifique Unite Mixte de Recherche 3347,F-91405 Orsay, France,Universite Paris Sud-11, F-91405 Orsay, France;

    Institut Curie, Institut National de la Sante et de la Recherche Medicale U1021, Centre National de la Recherche Scientifique Unite Mixte de Recherche 3347,F-91405 Orsay, France,Universite Paris Sud-11, F-91405 Orsay, France;

  • 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

    Pax3; Zic1; Hairy2; Msx1; Xenopus embryo;

    机译:Pax3;Zic1;Hairy2;Msx1;非洲爪蟾胚胎;

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