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

Autor:	Camacho-Aguilar E; Department of Biosciences, Rice University, Houston, TX 77005, USA. Electronic address: ecamagu@upo.es., Yoon ST; Department of Biosciences, Rice University, Houston, TX 77005, USA., Ortiz-Salazar MA; Department of Biosciences, Rice University, Houston, TX 77005, USA., Du S; Department of Biosciences, Rice University, Houston, TX 77005, USA., Guerra MC; Department of Biosciences, Rice University, Houston, TX 77005, USA., Warmflash A; Department of Biosciences, Rice University, Houston, TX 77005, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA. Electronic address: aryeh.warmflash@rice.edu.
Jazyk:	angličtina
Zdroj:	Cell systems [Cell Syst] 2024 May 15; Vol. 15 (5), pp. 445-461.e4. Date of Electronic Publication: 2024 Apr 30.
DOI:	10.1016/j.cels.2024.04.001
Abstrakt:	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. Competing Interests: Declaration of interests A.W. is a cofounder of and holds equity in Simbryo Technologies. The work presented here is not related to the interests of this commercial entity. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu