scholarly journals Autonomous Boolean modelling of developmental gene regulatory networks

2013 ◽  
Vol 10 (78) ◽  
pp. 20120574 ◽  
Author(s):  
Xianrui Cheng ◽  
Mengyang Sun ◽  
Joshua E. S. Socolar

During early embryonic development, a network of regulatory interactions among genes dynamically determines a pattern of differentiated tissues. We show that important timing information associated with the interactions can be faithfully represented in autonomous Boolean models in which binary variables representing expression levels are updated in continuous time, and that such models can provide a direct insight into features that are difficult to extract from ordinary differential equation (ODE) models. As an application, we model the experimentally well-studied network controlling fly body segmentation. The Boolean model successfully generates the patterns formed in normal and genetically perturbed fly embryos, permits the derivation of constraints on the time delay parameters, clarifies the logic associated with different ODE parameter sets and provides a platform for studying connectivity and robustness in parameter space. By elucidating the role of regulatory time delays in pattern formation, the results suggest new types of experimental measurements in early embryonic development.

2018 ◽  
Vol 15 (142) ◽  
pp. 20180157 ◽  
Author(s):  
Karen M. Page ◽  
Ruben Perez-Carrasco

Ring oscillators are biochemical circuits consisting of a ring of interactions capable of sustained oscillations. The nonlinear interactions between genes hinder the analytical insight into their function, usually requiring computational exploration. Here, we show that, despite the apparent complexity, the stability of the unique steady state in an incoherent feedback ring depends only on the degradation rates and a single parameter summarizing the feedback of the circuit. Concretely, we show that the range of regulatory parameters that yield oscillatory behaviour is maximized when the degradation rates are equal. Strikingly, this result holds independently of the regulatory functions used or number of genes. We also derive properties of the oscillations as a function of the degradation rates and number of nodes forming the ring. Finally, we explore the role of mRNA dynamics by applying the generic results to the specific case with two naturally different degradation timescales.


2008 ◽  
Vol 4 (1) ◽  
Author(s):  
Jens Weingärtner ◽  
Kristina Lotz ◽  
Andreas Faltermeier ◽  
Oliver Driemel ◽  
Johannes Kleinheinz ◽  
...  

2020 ◽  
Vol 102 (4) ◽  
pp. 795-805 ◽  
Author(s):  
Sandeep K Rajput ◽  
Chunyan Yang ◽  
Mohamed Ashry ◽  
Joseph K Folger ◽  
Jason G Knott ◽  
...  

Abstract Characterization of the molecular factors regulating early embryonic development and their functional mechanisms is critical for understanding the causes of early pregnancy loss in monotocous species (cattle, human). We previously characterized a stage specific functional role of follistatin, a TGF-beta superfamily binding protein, in promoting early embryonic development in cattle. The mechanism by which follistatin mediates this embryotropic effect is not precisely known as follistatin actions in cattle embryos are independent of its classically known activin inhibition activity. Apart from activin, follistatin is known to bind and modulate the activity of the bone morphogenetic proteins (BMPs), which signal through SMAD1/5 pathway and regulate several aspects of early embryogenesis in other mammalian species. Present study was designed to characterize the activity and functional requirement of BMP signaling during bovine early embryonic development and to investigate if follistatin involves BMP signaling for its stage specific embryotropic actions. Immunostaining and western blot analysis demonstrated that SMAD1/5 signaling is activated after embryonic genome activation in bovine embryos. However, days 1–3 follistatin treatment reduced the abundance of phosphorylated SMAD1/5 in cultured embryos. Inhibition of active SMAD1/5 signaling (8–16 cell to blastocyst) using pharmacological inhibitors and/or lentiviral-mediated inhibitory SMAD6 overexpression showed that SMAD1/5 signaling is required for blastocyst production, first cell lineage determination as well as mRNA and protein regulation of TE (CDX2) cell markers. SMAD1/5 signaling was also found to be essential for embryotropic actions of follistatin during days 4–7 but not days 1–3 of embryo development suggesting a role for follistatin in regulation of SMAD1/5 signaling in bovine embryos.


2015 ◽  
Vol 31 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Gui-Dong Yao ◽  
Sen-Lin Shi ◽  
Wen-Yan Song ◽  
Hai-Xia Jin ◽  
Zhao-Feng Peng ◽  
...  

2009 ◽  
Vol 81 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Jyothsna Tejomurtula ◽  
Kyung-Bon Lee ◽  
Swamy K. Tripurani ◽  
George W. Smith ◽  
Jianbo Yao

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