A functional genome-wide in vivo screen identifies new regulators of signalling pathways during early Xenopus embryogenesis.
A functional genome-wide in vivo screen identifies new regulators of signalling pathways during early Xenopus embryogenesis.
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DOI：
10.1371/journal.pone.0079469
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dorey K
中科院分区：
文献类型：
--
作者：
Zhang S;Li J;Lea R;Amaya E;Dorey K
胚胎发育需要对几个基本过程进行精确的调控，如组织和器官的图案化、细胞命运决定和形态发生。有趣的是，这些不同的过程仅由少数信号通路控制，并且这些通路中的一个或多个的错误调节可能导致各种先天性缺陷和疾病。因此，研究这些信号通路如何在分子水平上调节对于理解脊椎动物胚胎发生的机制以及开发人类疾病的治疗方法至关重要。在这里，我们设计并在非洲爪蟾胚胎中进行了大规模的功能获得筛选，旨在鉴定MAPK/Erk，PI 3 K/Akt，BMP和TGF-β/Nodal信号通路的新调节剂。我们的功能获得性筛选是基于对改变关键信号分子磷酸化状态的基因产物的鉴定，这些信号分子报告通路的激活状态。总的来说，我们已经确定了20个新的分子，调节活动的一个或多个信号通路在早期非洲爪蟾的发展。这是第一次进行这样的功能筛选，这些发现为更全面地了解在正常和病理条件下调节重要信号通路活性的分子机制铺平了道路。
Embryonic development requires exquisite regulation of several essential processes, such as patterning of tissues and organs, cell fate decisions, and morphogenesis. Intriguingly, these diverse processes are controlled by only a handful of signalling pathways, and mis-regulation in one or more of these pathways may result in a variety of congenital defects and diseases. Consequently, investigating how these signalling pathways are regulated at the molecular level is essential to understanding the mechanisms underlying vertebrate embryogenesis, as well as developing treatments for human diseases. Here, we designed and performed a large-scale gain-of-function screen in Xenopus embryos aimed at identifying new regulators of MAPK/Erk, PI3K/Akt, BMP, and TGF-β/Nodal signalling pathways. Our gain-of-function screen is based on the identification of gene products that alter the phosphorylation state of key signalling molecules, which report the activation state of the pathways. In total, we have identified 20 new molecules that regulate the activity of one or more signalling pathways during early Xenopus development. This is the first time that such a functional screen has been performed, and the findings pave the way toward a more comprehensive understanding of the molecular mechanisms regulating the activity of important signalling pathways under normal and pathological conditions.
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DOI：
10.1242/dev.037689
发表时间：
2010-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Dorey K;Amaya E
通讯作者：
Amaya E
影响因子：
11.4
作者：
Greenberg, A. J.;Lee, A. M.;Serie, D. J.;McDonnell, S. K.;Cerhan, J. R.;Liebow, M.;Larson, D. R.;Colby, C. L.;Norman, A. D.;Kyle, R. A.;Kumar, S.;Rajkumar, S. V.;Diasio, R. B.;Slager, S. L.;Vachon, C. M.
通讯作者：
Vachon, C. M.
影响因子：
64.8
作者：
Bouwmeester, T;Kim, SH;DeRobertis, EM
通讯作者：
DeRobertis, EM
DOI：
10.1016/s1357-2725(01)00150-9
发表时间：
2002-06-01
影响因子：
4
作者：
Aerbajinai, W;Ishihara, T;Tsukahara, T
通讯作者：
Tsukahara, T
影响因子：
2.7
作者：
Callery, Elizabeth M.;Thomsen, Gerald H.;Smith, James C.
通讯作者：
Smith, James C.