Live Visualization of ERK Activity in the Mouse Blastocyst Reveals Lineage-Specific Signaling Dynamics.
Live Visualization of ERK Activity in the Mouse Blastocyst Reveals Lineage-Specific Signaling Dynamics.
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DOI：
10.1016/j.devcel.2020.09.030
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发表时间：
2020-11-09
影响因子：
11.8
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
--
作者：
Simon CS;Rahman S;Raina D;Schröter C;Hadjantonakis AK
FGF/ERK 信号传导对于小鼠囊胚细胞谱系的形成和增殖至关重要。然而，ERK 信号动力学从未在活胚胎中直接观察到。为了解决差异信号传导是否与特定细胞命运和状态相关的问题，我们生成了表达 ERK 激酶易位报告基因 (KTR) 的靶向小鼠品系，该小鼠品系能够以单细胞分辨率实时定量 ERK 活性。该生物传感器在胚胎中的 3D 延时成像揭示了滋养外胚层在明显的极性分化与壁分化之前的空间分级 ERK 活性。在内细胞团 (ICM) 内，所有细胞都以不同的持续时间和强度传递 FGF/ERK 信号。原始内胚层细胞表现出较高的 ERK 活性总体水平，而多能外胚层细胞则表现出较低的基础活性和零星脉冲。这些结果构成了哺乳动物植入前发育过程中信号事件的直接可视化，并揭示了空间和时间谱系特定动态的存在。 FGF/ERK 信号传导对于小鼠囊胚细胞谱系的形成和增殖至关重要。 Simon 等人使用 ERK 激酶易位生物传感器。显示滋养外胚层的 ERK 活性空间分级，原始内胚层和外胚层细胞具有不同的 ERK 动态。
FGF/ERK signaling is crucial for the patterning and proliferation of cell lineages that comprise of the mouse blastocyst. However, ERK signaling dynamics have never been directly visualized in live embryos. To address whether differential signaling is associated with particular cell fates and states, we generated a targeted mouse line expressing an ERK-kinase translocation reporter (KTR) that enables live quantification of ERK activity at single cell resolution. 3D time-lapse imaging of this biosensor in embryos revealed spatially graded ERK activity in the trophectoderm prior to overt polar-versus-mural differentiation. Within the inner cell mass (ICM), all cells relayed FGF/ERK signals with varying durations and magnitude. Primitive endoderm cells displayed higher overall levels of ERK activity, while pluripotent epiblast cells exhibited lower basal activity with sporadic pulses. These results constitute a direct visualization of signaling events during mammalian pre-implantation development and reveal the existence of spatial and temporal lineage specific dynamics. FGF/ERK signaling is crucial for the patterning and proliferation of cell lineages that comprise of the mouse blastocyst. Using an ERK -kinase translocation biosensor, Simon et al. show the trophectoderm is patterned by spatially graded ERK activity, and primitive endoderm and epiblast cells have distinct ERK dynamics.
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影响因子：
10.5
作者：
Brewer JR;Molotkov A;Mazot P;Hoch RV;Soriano P
通讯作者：
Soriano P
影响因子：
5.2
作者：
Artus, Jerome;Kang, Minjung;Cohen-Tannoudji, Michel;Hadjantonakis, Anna-Katerina
通讯作者：
Hadjantonakis, Anna-Katerina
影响因子：
10.5
作者：
Brewer JR;Mazot P;Soriano P
通讯作者：
Soriano P
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
1.5
作者：
Goldin, SN;Papaioannou, VE
通讯作者：
Papaioannou, VE