原始条纹
生物
Wnt信号通路
计算生物学
进化生物学
细胞生物学
口译(哲学)
遗传学
计算机科学
原肠化
胚胎
信号转导
胚胎发生
程序设计语言
作者
Elena Camacho-Aguilar,Sumin Yoon,Miguel Angel Ortiz-Salazar,Siqi Du,Guerra Mc,Aryeh Warmflash
标识
DOI:10.1016/j.cels.2024.04.001
摘要
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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