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通过转基因斑马鱼揭示动态 Smad 介导的 BMP 信号通路。

Dynamic smad-mediated BMP signaling revealed through transgenic zebrafish.

机构信息

Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

出版信息

Dev Dyn. 2011 Mar;240(3):712-22. doi: 10.1002/dvdy.22567. Epub 2011 Feb 8.

Abstract

Bone morphogenic protein (BMP) signaling is fundamental to development, injury response, and homeostasis. We have developed transgenic zebrafish that report Smad-mediated BMP signaling in embryos and adults. These lines express either enhanced green fluorescent protein (eGFP), destabilized eGFP, or destabilized Kusabira Orange 2 (KO2) under the well-characterized BMP Response Element (BRE). These fluorescent proteins were found to be expressed dynamically in regions of known BMP signaling including the developing tail bud, hematopoietic lineage, dorsal eye, brain structures, heart, jaw, fins, and somites, as well as other tissues. Responsiveness to changes in BMP signaling was confirmed by observing fluorescence after activation in an hsp70:bmp2b transgenic background or by inhibition in an hsp70:nog3 background. We further demonstrated faithful reportage by the BRE transgenic lines following chemical repression of BMP signaling using an inhibitor of BMP receptor activity, dorsomorphin. Overall, these lines will serve as valuable tools to explore the mechanisms and regulation of BMP signal during embryogenesis, in tissue maintenance, and during disease.

摘要

骨形态发生蛋白 (BMP) 信号转导对于胚胎发育、损伤反应和内稳态至关重要。我们开发了一种转基因斑马鱼,该鱼能够报告胚胎和成鱼中 Smad 介导的 BMP 信号转导。这些品系在特征明确的 BMP 反应元件 (BRE) 下表达增强型绿色荧光蛋白 (eGFP)、不稳定 eGFP 或不稳定 Kusabira Orange 2 (KO2)。这些荧光蛋白在已知的 BMP 信号转导区域(包括正在发育的尾芽、造血谱系、背眼、脑结构、心脏、下颚、鳍和体节以及其他组织)中动态表达。在 hsp70:bmp2b 转基因背景下观察到激活后的荧光或在 hsp70:nog3 背景下观察到抑制后的荧光,证实了对 BMP 信号转导变化的反应性。我们进一步通过使用 BMP 受体活性抑制剂 dorsomorphin 抑制 BMP 信号转导,证明了 BRE 转基因系的忠实报告。总体而言,这些系将成为探索胚胎发生、组织维持和疾病期间 BMP 信号转导机制和调控的有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/3072245/2b4bba1894a3/nihms265816f1.jpg

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本文引用的文献

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Recent advances in BMP receptor signaling.BMP 受体信号转导的最新进展。
Cytokine Growth Factor Rev. 2009 Oct-Dec;20(5-6):343-55. doi: 10.1016/j.cytogfr.2009.10.007. Epub 2009 Nov 7.
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Bone morphogenetic protein receptors and signal transduction.骨形态发生蛋白受体与信号转导。
J Biochem. 2010 Jan;147(1):35-51. doi: 10.1093/jb/mvp148. Epub 2009 Sep 17.

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