Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network
Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network
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DOI：
10.1073/pnas.1010740107
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发表时间：
2011-01-04
影响因子：
11.1
通讯作者：
Monsoro-Burq, Anne H.
中科院分区：
文献类型：
--
作者：
de Croze, Noemie;Maczkowiak, Frederique;Monsoro-Burq, Anne H.
神经嵴（NC）出现在其祖域，神经边界（NB）内发生的组合诱导事件。一些转录因子在NB的早期起作用，但起始分子事件仍然难以捉摸。最近的数据表明，从基础脊椎动物的AP 2可能是至关重要的NC出现，但是，AP 2因子在NB的作用仍然不清楚。我们在这里表明，AP 2a启动NB图案，并足以引起神经化外胚层的NB样模式。相比之下，其他早期调节因子不参与NB处的ap 2a起始，而是合作以进一步建立稳健的NB模式。NC调节网络使用分泌的诱导物和转录因子的多步级联，首先在NB处，然后在NC祖细胞内。在这里，我们报告说，AP 2a在这个级联的两个不同的步骤。作为已知最早的NB指定，AP 2a介导Wnt信号启动NB和激活pax 3;作为NC指定，AP 2a调节独立于NB图案化和下游的NC进一步发展。我们的发现调和了各种脊椎动物生物体的相互矛盾的观察结果。AP 2a为多功能分子的重复使用提供了范例，从而促进了NC在脊椎动物中的出现。
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.