An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development.
An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development.
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DOI：
10.1016/j.devcel.2023.08.021
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发表时间：
2023-12-04
影响因子：
11.8
通讯作者：
Hill CS
中科院分区：
文献类型：
--
作者：
Wilcockson SG;Guglielmi L;Araguas Rodriguez P;Amoyel M;Hill CS
细胞外信号调节激酶 (Erk) 信号动力学在各种情况下引发不同的细胞反应。早期斑马鱼胚胎是探索体内 Erk 信号动力学作用的理想模型，因为囊胚边缘的成纤维细胞生长因子 (Fgf) 信号传导会诱导激活的二磷酸化 Erk (P-Erk) 梯度。在这里，我们描述了一种改进的 Erk 特异性生物传感器，我们将其称为改良的 Erk 激酶易位报告基因 (modErk-KTR)。我们展示了这种生物传感器在体外以及在斑马鱼和果蝇胚胎发育中的实用性。此外，我们发现 Fgf/Erk 信号传导是动态的，并且在早期斑马鱼和果蝇发育过程中与组织生长相关。 Erk 活性在有丝分裂之前迅速消失，我们将其称为有丝分裂擦除，诱导不活动期，从而为异步分裂的组织提供异质性来源。我们改良的报告基因和转基因系代表了研究体内 Erk 信号动力学作用的重要资源。
Extracellular signal-regulated kinase (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 fibroblast growth factor (Fgf) signaling at the blastula 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. Erk activity 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.
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影响因子：
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作者：
Guglielmi L;Heliot C;Kumar S;Alexandrov Y;Gori I;Papaleonidopoulou F;Barrington C;East P;Economou AD;French PMW;McGinty J;Hill CS
通讯作者：
Hill CS
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