mathematicalmodelingrevealsthemechanismsoffeedforwardregulationincellfatedecisionsinbuddingyeast

	mathematicalmodelingrevealsthemechanismsoffeedforwardregulationincellfatedecisionsinbuddingyeast
	Li Wenlong 1; Yi Ming 2; Zou Xiufen 1
刊名	quantitativebiology
	2015
卷号	3 期号:2 页码:55
ISSN号	2095-4689
英文摘要	The determination of cell fate is one of the key questions of developmental biology. Recent experiments showed that feedforward regulation is a novel feature of regulatory networks that controls reversible cellular transitions. However, the underlying mechanism of feedforward regulation-mediated cell fate decision is still unclear. Therefore,using experimental data, we develop a full mathematical model of the molecular network responsible for cell fate selection in budding yeast. To validate our theoretical model, we first investigate the dynamical behaviors of key proteins at the Start transition point and the G1/S transition point; a crucial three-node motif consisting of cyclin(Cln1/2), Substrate/Subunit Inhibitor of cyclin-dependent protein kinase (Sic1) and cyclin B (Clb5/6) is considered at these points. The rapid switches of these important components between high and low levels at two transition check points are demonstrated reasonably by our model. Many experimental observations about cell fate decision and cell size control are also theoretically reproduced. Interestingly, the feedforward regulation provides a reliable separation between different cell fates. Next, our model reveals that the threshold for the amount of WHIskey (Whi5) removed from the nucleus is higher at the Reentry point in pheromone-arrested cells compared with that at the Start point in cycling cells. Furthermore, we analyze the hysteresis in the cell cycle kinetics in response to changes in pheromone concentration, showing that Cln3 is the primary driver of reentry and Cln1/2 is the secondary driver of reentry. In particular, we demonstrate that the inhibition of Cln1/2 due to the accumulation of Factor ARrest (Far1) directly reinforces arrest. Finally, theoretical work verifies that the three-node coherent feedforward motif created by cell FUSion (Fus3), Far1 and STErile (Ste12) ensures the rapid arrest and reversibility of a cellular state. The combination of our theoretical model and the previous experimental data contributes to the understanding of the molecular mechanisms of the cell fate decision at the G1 phase in budding yeast and will stimulate further biological experiments in future.
语种	英语
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/19427]
专题	中国科学院武汉物理与数学研究所
作者单位	1.武汉大学 2.中国科学院武汉物理与数学研究所
推荐引用方式 GB/T 7714	Li Wenlong,Yi Ming,Zou Xiufen. mathematicalmodelingrevealsthemechanismsoffeedforwardregulationincellfatedecisionsinbuddingyeast[J]. quantitativebiology,2015,3(2):55.
APA	Li Wenlong,Yi Ming,&Zou Xiufen.(2015).mathematicalmodelingrevealsthemechanismsoffeedforwardregulationincellfatedecisionsinbuddingyeast.quantitativebiology,3(2),55.
MLA	Li Wenlong,et al."mathematicalmodelingrevealsthemechanismsoffeedforwardregulationincellfatedecisionsinbuddingyeast".quantitativebiology 3.2(2015):55.