Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.
Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.
Dev Biol. 2023 Nov;503:113-119. doi: 10.1016/j.ydbio.2023.08.007. Epub 2023 Sep 1.
Understanding how cells activate intracellular signaling pathways in response to external signals, such as growth factors, is a longstanding goal of cell and developmental biology. Recently, live-cell signaling reporters have greatly expanded our understanding of signaling dynamics in response to wide-ranging stimuli and chemical or genetic perturbation, both ex vivo (cell lines) and in vivo (whole embryos or animals). Among the many varieties of reporter systems, translocation reporters that change sub-cellular localization in response to pathway activation have received considerable attention for their ease of use compared to FRET systems and favorable response times compared to transcriptional reporters. We reasoned that mouse reporter lines expressed in a conditional fashion would be a useful addition to the arsenal of mouse genetic tools, as such lines remain undeveloped despite widespread use of these sensors. We therefore created and validated two novel mouse reporter lines at the ROSA26 locus. One expresses an ERK1/2 pathway reporter and a nuclear marker from a single transcript, while the second additionally expresses an AKT reporter in order to simultaneously interrogate both pathways.
了解细胞如何响应外部信号(如生长因子)激活细胞内信号通路,是细胞和发育生物学的长期目标。最近,活细胞信号报告器极大地扩展了我们对信号动力学的理解,包括对广泛刺激以及化学或遗传扰动的反应,无论是在体(细胞系)还是在体(整个胚胎或动物)。在许多报告器系统中,与 FRET 系统相比,易操作性以及与转录报告器相比,响应时间的优势,使得对通路激活做出亚细胞定位改变的转位报告器受到了相当多的关注。我们推断,以条件方式表达的小鼠报告系将成为小鼠遗传工具库的有用补充,尽管这些传感器得到了广泛应用,但这些报告系仍然没有得到开发。因此,我们在 ROSA26 基因座上创建并验证了两个新的小鼠报告系。一个报告系从单个转录本中表达 ERK1/2 通路报告器和核标记物,而第二个报告系则另外表达 AKT 报告器,以便同时检测两条通路。