An improved Erk biosensor reveals oscillatory Erk dynamics driven by mitotic erasure during early development
An improved Erk biosensor reveals oscillatory Erk dynamics driven by mitotic erasure during early development
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DOI：
10.1101/2022.11.03.515001
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发表时间：
2022-11
期刊：
影响因子：
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通讯作者：
Scott G. Wilcockson;Luca Guglielmi;Pablo Araguas Rodriguez;M. Amoyel;C. Hill
中科院分区：
文献类型：
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作者：
Scott G. Wilcockson;Luca Guglielmi;Pablo Araguas Rodriguez;M. Amoyel;C. Hill
Erk信号传导动力学在各种情况下引起不同的细胞反应。早期斑马鱼胚胎是探索Erk信号动力学在体内作用的理想模型，因为Fgf信号在囊胚胚胎边缘诱导激活的二磷酸化Erk（P-Erk）的梯度。在这里，我们描述了一种改进的ERK特异性生物传感器，我们称之为修饰的ERK激酶易位报告（modErk-KTR）。我们证明了这种生物传感器在体外和斑马鱼和果蝇胚胎发育中的效用。此外，我们表明，FGF/ERK信号是动态的，并耦合到组织生长在早期斑马鱼和果蝇的发展。信号在有丝分裂之前迅速消失，我们称之为有丝分裂擦除，诱导不活动期，从而在异步分裂的组织中提供异质性的来源。我们的修改报告和转基因株系代表了一个重要的资源，询问的作用，Erk信号动力学在体内。
Erk signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by Fgf signaling at the blastula embryonic margin. Here we describe an improved Erk-specific biosensor which we term modified Erk Kinase Translocation Reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Signaling is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo.