Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.
Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.
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DOI：
10.1016/j.ydbio.2013.12.010
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发表时间：
2014-02-15
影响因子：
2.7
通讯作者：
Monsoro-Burq, Anne H.
中科院分区：
文献类型：
--
作者：
Plouhinec, Jean-Louis;Roche, Daniel D.;Pegoraro, Caterina;Figueiredo, Ana Leonor;Maczkowiak, Frederique;Brunet, Lisa J.;Milet, Cecile;Vert, Jean-Philippe;Pollet, Nicolas;Harland, Richard M.;Monsoro-Burq, Anne H.
神经嵴发育是由一个复杂且仍知之甚少的基因调控网络精心策划的。通过信号分子和转录因子（例如 AP2、Gbx2、Pax3 和 Zic1）的联合作用，在神经板的外侧缘诱导迁移前神经嵴。其中，Pax3和Zic1对于触发完整的神经嵴发育程序都是必要且充分的。然而，它们在神经嵴调节网络中的基因目标仍然未知。在这里，通过对青蛙显微解剖神经边界的转录组分析，我们确定了迁徙前神经嵴的扩展基因特征，并定义了调节网络的新潜在成员。该特征包括 34 个新基因，以及 44 个在神经边界表达的已知基因。使用另一项结合 Pax3 和 Zic1 功能获得和蛋白质翻译阻断的微阵列分析，我们发现了该特征中的 25 个 Pax3 和 Zic1 直接靶标。我们证明了神经边界指定符 Pax3 和 Zic1 是神经嵴指定符 Snail1/2、Foxd3、Twist1 和 Tfap2b 的直接上游调节因子。此外，它们还可以通过诱导关键通路调节因子（Axin2 和 Cyp26c1）来调节参与神经嵴发育的多个信号通路（Wnt、视黄酸）的转录输出。我们还发现 Pax3 可以通过正向自动调节反馈循环维持其自身的表达。这些分层感应、反馈循环和通路调制提供了理解神经嵴感应网络的新工具。
Neural crest development is orchestrated by a complex and still poorly understood gene regulatory network. Premigratory neural crest is induced at the lateral border of the neural plate by the combined action of signaling molecules and transcription factors such as AP2, Gbx2, Pax3 and Zic1. Among them, Pax3 and Zic1 are both necessary and sufficient to trigger a complete neural crest developmental program. However, their gene targets in the neural crest regulatory network remain unknown. Here, through a transcriptome analysis of frog microdissected neural border, we identified an extended gene signature for the premigratory neural crest, and we defined novel potential members of the regulatory network. This signature includes 34 novel genes, as well as 44 known genes expressed at the neural border. Using another microarray analysis which combined Pax3 and Zic1 gain-of-function and protein translation blockade, we uncovered 25 Pax3 and Zic1 direct targets within this signature. We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b. In addition, they may modulate the transcriptional output of multiple signaling pathways involved in neural crest development (Wnt, Retinoic Acid) through the induction of key pathway regulators (Axin2 and Cyp26c1). We also found that Pax3 could maintain its own expression through a positive autoregulatory feedback loop. These hierarchical inductions, feedback loops, and pathway modulations provide novel tools to understand the neural crest induction network.
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影响因子：
4.5
作者：
Hertzano R;Elkon R;Kurima K;Morrisson A;Chan SL;Sallin M;Biedlingmaier A;Darling DS;Griffith AJ;Eisenman DJ;Strome SE
通讯作者：
Strome SE
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
2.7
作者：
Chang, CB;Hemmati-Brivanlou, A
通讯作者：
Hemmati-Brivanlou, A
小鼠端脑发育过程中原神经基因调控网络的表征。
影响因子：
5.4
作者：
Gohlke JM;Armant O;Parham FM;Smith MV;Zimmer C;Castro DS;Nguyen L;Parker JS;Gradwohl G;Portier CJ;Guillemot F
通讯作者：
Guillemot F
DOI：
10.1073/pnas.1010740107
发表时间：
2011-01-04
影响因子：
11.1
作者：
de Croze, Noemie;Maczkowiak, Frederique;Monsoro-Burq, Anne H.
通讯作者：
Monsoro-Burq, Anne H.