Combinatorial interpretation of BMP and WNT controls the decision between primitive streak and extraembryonic fates

IF 9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Systems Pub Date : 2024-04-30 DOI:10.1016/j.cels.2024.04.001
Elena Camacho-Aguilar, Sumin T. Yoon, Miguel A. Ortiz-Salazar, Siqi Du, M. Cecilia Guerra, Aryeh Warmflash
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Abstract

BMP signaling is essential for mammalian gastrulation, as it initiates a cascade of signals that control self-organized patterning. As development is highly dynamic, it is crucial to understand how time-dependent combinatorial signaling affects cellular differentiation. Here, we show that BMP signaling duration is a crucial control parameter that determines cell fates upon the exit from pluripotency through its interplay with the induced secondary signal WNT. BMP signaling directly converts cells from pluripotent to extraembryonic fates while simultaneously upregulating Wnt signaling, which promotes primitive streak and mesodermal specification. Using live-cell imaging of signaling and cell fate reporters together with a simple mathematical model, we show that this circuit produces a temporal morphogen effect where, once BMP signal duration is above a threshold for differentiation, intermediate and long pulses of BMP signaling produce specification of mesoderm and extraembryonic fates, respectively. Our results provide a systems-level picture of how these signaling pathways control the landscape of early human development.

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BMP和WNT的组合解释控制着原始条纹和胚外命运之间的抉择
BMP 信号对哺乳动物的胃形成至关重要,因为它启动了一连串控制自组织形态的信号。由于发育是高度动态的,因此了解随时间变化的组合信号如何影响细胞分化至关重要。在这里,我们展示了 BMP 信号持续时间是一个关键的控制参数,它通过与诱导次级信号 WNT 的相互作用,决定了细胞从多能状态退出时的命运。BMP信号直接将细胞从多能性转化为胚外型,同时上调Wnt信号,促进原始条纹和中胚层的规范化。通过对信号传导和细胞命运报告的活细胞成像以及一个简单的数学模型,我们发现这一回路产生了一种时间形态发生器效应,一旦 BMP 信号持续时间超过分化阈值,BMP 信号的中脉冲和长脉冲就会分别产生中胚层和胚外命运的规格化。我们的研究结果提供了一幅系统水平的图景,展示了这些信号通路是如何控制人类早期发育的。
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来源期刊
Cell Systems
Cell Systems Medicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍: In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.
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