A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning.

A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning.
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DOI:
10.1016/j.ydbio.2017.08.015
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发表时间:
2017-10-15
影响因子:
2.7
通讯作者:
Martindale MQ
Martindale MQ
中科院分区:
生物学3区
文献类型:
--
作者:
Amiel AR;Johnston H;Chock T;Dahlin P;Iglesias M;Layden M;Röttinger E;Martindale MQ

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胚层形成和轴向模式是大多数后生动物胚胎发育过程中紧密联系的生物学过程。除了典型的WNT外,有人提出ERK-MAPK信号也参与了刺胞动物口腔和流产区域的指定。然而,后一种现象的效应和分子机制尚不清楚。通过筛选ERK-MAPK信号在这两个区域的潜在效应,我们确定了ETS转录因子家族的成员Nverg,它在原肠形成之前双极性表达。我们进一步描述了NvERG在原肠胚形成、内胚层以及顶端结构域形成中的关键作用。使用先前描述的以及新的潜在下游靶点获得的NvERG敲低表型的分子特征提供了证据,证明单个转录因子NvERG同时控制两组不同的下游靶点的表达,导致发育胚胎的相反极性产生两个不同的胚胎基因调控网络(grn)。我们还强调了cWNT和MEK/ERK/ERG信号的分子相互作用,这为线虫的胚胎轴向组织提供了新的见解,并显示了cWNT抑制MEK/ERK/ERG信号在两个亚域内内膜分离中的作用,而这两种途径的共同输入是正确的顶端结构域形成所必需的。总之,我们构建了全球刺胞动物胚胎GRN的第一个蓝图,这是解决胚胎和幼虫发育进化的其他基因特异性研究的基础。
Germ layer formation and axial patterning are biological processes that are tightly linked during embryonic development of most metazoans. In addition to canonical WNT, it has been proposed that ERK-MAPK signaling is involved in specifying oral as well as aboral territories in cnidarians. However, the effector and the molecular mechanism underlying latter phenomenon is unknown. By screening for potential effectors of ERK-MAPK signaling in both domains, we identified a member of the ETS family of transcription factors, Nverg that is bi-polarily expressed prior to gastrulation. We further describe the crucial role of NvERG for gastrulation, endomesoderm as well as apical domain formation. The molecular characterization of the obtained NvERG knock-down phenotype using previously described as well as novel potential downstream targets, provides evidence that a single transcription factor, NvERG, simultaneously controls expression of two different sets of downstream targets, leading to two different embryonic gene regulatory networks (GRNs) in opposite poles of the developing embryo. We also highlight the molecular interaction of cWNT and MEK/ERK/ERG signaling that provides novel insight into the embryonic axial organization of Nematostella, and show a cWNT repressive role of MEK/ERK/ERG signaling in segregating the endomesoderm in two sub-domains, while a common input of both pathways is required for proper apical domain formation. Taking together, we build the first blueprint for a global cnidarian embryonic GRN that is the foundation for additional gene specific studies addressing the evolution of embryonic and larval development.
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