scholarly journals Dynamic positioning and precision of bistable gene expression boundaries through diffusion and morphogen decay

2020 ◽  
Author(s):  
Melinda Liu Perkins
Keyword(s):  
Gene Expression ◽  
Mathematical Theory ◽  
Initial Conditions ◽  
Propagation Speed ◽  
Positional Information ◽  
Future Research ◽  
Toggle Switch ◽  
Embryonic Patterning ◽  
Cell Coupling ◽  
Morphogen Gradients

1AbstractTraditional models for how morphogen gradients guide embryonic patterning fail to account for experimental observations of temporal refinement in gene expression domains. Dynamic positional information has recently emerged as a framework to address this shortcoming. Here, we explore two central aspects of dynamic positional information—the precision and placement of gene expression boundaries—in bistable genetic networks driven by morphogen gradients. First, we hypothesize that temporal morphogen decay may increase the precision of a boundary by compensating for variation in initial conditions that would otherwise lead neighboring cells with identical inputs to diverge to separate steady states. Second, we explore how diffusion of gene products may play a key role in placing gene expression boundaries. Using an existing model for Hb patterning in embryonic fruit flies, we show that diffusion permits boundaries to act as near-traveling wavefronts with local propagation speed determined by morphogen concentration. We then harness our understanding of near-traveling fronts to propose a method for achieving accurate steady-state boundary placement independent of initial conditions. Our work posits functional roles for temporally varying inputs and cell-to-cell coupling in the regulation and interpretation of dynamic positional information, illustrating that mathematical theory should serve to clarify not just our quantitative, but also our intuitive understanding of patterning processes.2Author SummaryIn many developmental systems, cells interpret spatial gradients of chemical morphogens to produce gene expression boundaries in exact positions. The simplest mathematical models for “positional information” rely on threshold detection, but such models are not robust to variations in the morphogen gradient or initial protein concentrations. Furthermore, these models fail to account for experimental results showing dynamic shifts in boundary placement and increased boundary precision over time. Here, we propose two theoretical mechanisms for enhancing boundary precision and placement using a bistable toggle switch. Distinct from existing research in “dynamic positional information”, this work posits a functional role for temporal decay in morphogen concentration and for diffusion of gene expression products, the latter of which is often omitted in quantitative models. We suggest that future research into dynamic positional information would benefit from perspectives that link local (cellular) and global (patterning) behaviors, as well as from mathematical theory that builds our intuitive understanding alongside more data-driven approaches.

scholarly journals Implications of diffusion and time-varying morphogen gradients for the dynamic positioning and precision of bistable gene expression boundaries

2021 ◽  
Vol 17 (6) ◽  
pp. e1008589
Author(s):  
Melinda Liu Perkins
Keyword(s):  
Gene Expression ◽  
Initial Conditions ◽  
Positional Information ◽  
Fruit Fly ◽  
Time Varying ◽  
Gene Products ◽  
Embryonic Patterning ◽  
Morphogen Gradients ◽  
Pde Model ◽  
Gradient Evolution

The earliest models for how morphogen gradients guide embryonic patterning failed to account for experimental observations of temporal refinement in gene expression domains. Following theoretical and experimental work in this area, dynamic positional information has emerged as a conceptual framework to discuss how cells process spatiotemporal inputs into downstream patterns. Here, we show that diffusion determines the mathematical means by which bistable gene expression boundaries shift over time, and therefore how cells interpret positional information conferred from morphogen concentration. First, we introduce a metric for assessing reproducibility in boundary placement or precision in systems where gene products do not diffuse, but where morphogen concentrations are permitted to change in time. We show that the dynamics of the gradient affect the sensitivity of the final pattern to variation in initial conditions, with slower gradients reducing the sensitivity. Second, we allow gene products to diffuse and consider gene expression boundaries as propagating wavefronts with velocity modulated by local morphogen concentration. We harness this perspective to approximate a PDE model as an ODE that captures the position of the boundary in time, and demonstrate the approach with a preexisting model for Hunchback patterning in fruit fly embryos. We then propose a design that employs antiparallel morphogen gradients to achieve accurate boundary placement that is robust to scaling. Throughout our work we draw attention to tradeoffs among initial conditions, boundary positioning, and the relative timescales of network and gradient evolution. We conclude by suggesting that mathematical theory should serve to clarify not just our quantitative, but also our intuitive understanding of patterning processes.

scholarly journals MorphoGraphX 2.0: Providing context for biological image analysis with positional information

2021 ◽  
Author(s):  
Sören Strauss ◽  
Adam Runions ◽  
Brendan Lane ◽  
Dennis Eschweiler ◽  
Namrata Bajpai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Local Coordinate System ◽  
Growth Dynamics ◽  
Positional Information ◽  
Molecular Networks ◽  
Coordinate Systems ◽  
Morphogen Gradients ◽  
Generalized Framework ◽  
Plausible Mechanism ◽  
Microscopy Data

Positional information is a central concept in developmental biology. In developing organs, positional information can be idealized as a local coordinate system that arises from morphogen gradients controlled by organizers at key locations. This offers a plausible mechanism for the integration of the molecular networks operating in individual cells into the spatially-coordinated multicellular responses necessary for the organization of emergent forms. Understanding how positional cues guide morphogenesis requires the quantification of gene expression and growth dynamics in the context of their underlying coordinate systems. Here we present recent advances in the MorphoGraphX software (Barbier de Reuille et al. eLife 2015;4:e05864) that implement a generalized framework to annotate developing organs with local coordinate systems. These coordinate systems introduce an organ-centric spatial context to microscopy data, allowing gene expression and growth to be quantified and compared in the context of the positional information thought to control them.

scholarly journals Interpretation of morphogen gradients by a synthetic bistable circuit

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Paul K. Grant ◽  
Gregory Szep ◽  
Om Patange ◽  
Jacob Halatek ◽  
Valerie Coppard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Computational Models ◽  
Positional Information ◽  
Spatial Average ◽  
Spatial Patterning ◽  
Mutual Inhibition ◽  
E Coli ◽  
Morphogen Gradients ◽  
Stable Domains

Abstract During development, cells gain positional information through the interpretation of dynamic morphogen gradients. A proposed mechanism for interpreting opposing morphogen gradients is mutual inhibition of downstream transcription factors, but isolating the role of this specific motif within a natural network remains a challenge. Here, we engineer a synthetic morphogen-induced mutual inhibition circuit in E. coli populations and show that mutual inhibition alone is sufficient to produce stable domains of gene expression in response to dynamic morphogen gradients, provided the spatial average of the morphogens falls within the region of bistability at the single cell level. When we add sender devices, the resulting patterning circuit produces theoretically predicted self-organised gene expression domains in response to a single gradient. We develop computational models of our synthetic circuits parameterised to timecourse fluorescence data, providing both a theoretical and experimental framework for engineering morphogen-induced spatial patterning in cell populations.

scholarly journals Validation of Reference Genes for Studying Different Abiotic Stresses in oat (Avena sativa L.) by RT-qPCR

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1272
Author(s):  
Judit Tajti ◽  
Magda Pál ◽  
Tibor Janda
Keyword(s):  
Gene Expression ◽  
Avena Sativa ◽  
Abiotic Stresses ◽  
Reference Genes ◽  
Nutritional Value ◽  
Tissue Type ◽  
Future Research ◽  
Experimental Conditions ◽  
Expression Studies ◽  
Gene Expression Studies

Oat (Avena sativa L.) is a widely cultivated cereal with high nutritional value and it is grown mainly in temperate regions. The number of studies dealing with gene expression changes in oat continues to increase, and to obtain reliable RT-qPCR results it is essential to establish and use reference genes with the least possible influence caused by experimental conditions. However, no detailed study has been conducted on reference genes in different tissues of oat under diverse abiotic stress conditions. In our work, nine candidate reference genes (ACT, TUB, CYP, GAPD, UBC, EF1, TBP, ADPR, PGD) were chosen and analysed by four statistical methods (GeNorm, Normfinder, BestKeeper, RefFinder). Samples were taken from two tissues (leaves and roots) of 13-day-old oat plants exposed to five abiotic stresses (drought, salt, heavy metal, low and high temperatures). ADPR was the top-rated reference gene for all samples, while different genes proved to be the most stable depending on tissue type and treatment combinations. TUB and EF1 were most affected by the treatments in general. Validation of reference genes was carried out by PAL expression analysis, which further confirmed their reliability. These results can contribute to reliable gene expression studies for future research in cultivated oat.

scholarly journals Immune modulators in disease: integrating knowledge from the biomedical literature and gene expression

2015 ◽  
Vol 23 (3) ◽  
pp. 617-626 ◽  
Author(s):  
Nophar Geifman ◽  
Sanchita Bhattacharya ◽  
Atul J Butte
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Biomedical Literature ◽  
Cytokine Gene Expression ◽  
Future Research ◽  
Cytokine Gene ◽  
Medical Subject Headings ◽  
Expression Arrays ◽  
Gene Expression Arrays ◽  
Subject Headings

Abstract Objective Cytokines play a central role in both health and disease, modulating immune responses and acting as diagnostic markers and therapeutic targets. This work takes a systems-level approach for integration and examination of immune patterns, such as cytokine gene expression with information from biomedical literature, and applies it in the context of disease, with the objective of identifying potentially useful relationships and areas for future research. Results We present herein the integration and analysis of immune-related knowledge, namely, information derived from biomedical literature and gene expression arrays. Cytokine-disease associations were captured from over 2.4 million PubMed records, in the form of Medical Subject Headings descriptor co-occurrences, as well as from gene expression arrays. Clustering of cytokine-disease co-occurrences from biomedical literature is shown to reflect current medical knowledge as well as potentially novel relationships between diseases. A correlation analysis of cytokine gene expression in a variety of diseases revealed compelling relationships. Finally, a novel analysis comparing cytokine gene expression in different diseases to parallel associations captured from the biomedical literature was used to examine which associations are interesting for further investigation. Discussion We demonstrate the usefulness of capturing Medical Subject Headings descriptor co-occurrences from biomedical publications in the generation of valid and potentially useful hypotheses. Furthermore, integrating and comparing descriptor co-occurrences with gene expression data was shown to be useful in detecting new, potentially fruitful, and unaddressed areas of research. Conclusion Using integrated large-scale data captured from the scientific literature and experimental data, a better understanding of the immune mechanisms underlying disease can be achieved and applied to research.

Control of gene expression using a red- and far-red light–responsive bi-stable toggle switch

2014 ◽  
Vol 9 (3) ◽  
pp. 622-632 ◽  
Author(s):  
Konrad Müller ◽  
Matias D Zurbriggen ◽  
Wilfried Weber
Keyword(s):  
Gene Expression ◽  
Red Light ◽  
Toggle Switch ◽  
Control Of Gene Expression

scholarly journals Expression of genes SBP and leginsulin in contrasting soybean seed coats

2016 ◽  
Vol 46 (10) ◽  
pp. 1695-1700
Author(s):  
Carlos André Bahry ◽  
Paulo Dejalma Zimmer
Keyword(s):  
Gene Expression ◽  
Seed Quality ◽  
Soybean Seed ◽  
Future Research ◽  
Expression Of Genes ◽  
New Information ◽  
Soybean Genotypes ◽  
Phases Of Development ◽  
Seed Coats ◽  
Early Phases

ABSTRACT: Evaluation of differential candidate gene expression in contrasting soybean seeds is an auxiliary tool in the partial elucidation of processes involved in seeds formation, as well as it contributes to the generation of new information that can be used in future research or in the development of r genetic superior constitutions. The aim of this study was to evaluate the expression of two candidate genes, SBP and leginsulin genes, possibly involved in seed quality, in contrasting coats of four soybean genotypes. Two cultivars of yellow soybeans were used, BMX Potência RR and CD 202, and two lines of black soybean, TP and IAC. Gene expression was evaluated using qPCR in seven stages of development from seed coats for four genotypes, at 25, 30, 35, 40, 45, 50, and 55 days after anthesis. The design was completely randomized, with three replications. Data were subjected to analysis of variance and means compared by Tukey's test at 5% probability. SBP and leginsulin gene have higher expression in the early phases of development from seed coats of BMX Potência RR cultivar, followed by the IAC line. These genotypes are therefore of interest for further research involving these genes.

scholarly journals Spatiotemporal control of gene expression boundaries using a feedforward loop

2019 ◽  
Author(s):  
Prasad U. Bandodkar ◽  
Hadel Al Asafen ◽  
Gregory T. Reeves
Keyword(s):  
Gene Expression ◽  
Biological Networks ◽  
Target Gene ◽  
Network Motif ◽  
Control Of Gene Expression ◽  
Intermediate Node ◽  
Morphogen Gradients ◽  
Spatially Distributed ◽  
Spatiotemporal Behavior ◽  
Spatiotemporal Control

AbstractA feed forward loop (FFL) is commonly observed in several biological networks. The FFL network motif has been mostly been studied with respect to variation of the input signal in time, with only a few studies of FFL activity in a spatially distributed system such as morphogen-mediated tissue patterning. However, most morphogen gradients also evolve in time. We studied the spatiotemporal behavior of a coherent FFL in two contexts: (1) a generic, oscillating morphogen gradient and (2) the dorsal-ventral patterning of the early Drosophila embryo by a gradient of the NF-κB homolog Dorsal with its early target Twist. In both models, we found features in the dynamics of the intermediate node – phase difference and noise filtering – that were largely independent of the parameterization of the models, and thus were functions of the structure of the FFL itself. In the Dorsal gradient model, we also found that the dynamics of Dorsal require maternal pioneering factor Zelda for proper target gene expression.

Genes that control dorsoventral polarity affect gene expression along the anteroposterior axis of the Drosophila embryo

Development ◽  
1987 ◽  
Vol 99 (3) ◽  
pp. 327-332 ◽  
Author(s):  
S.B. Carroll ◽  
G.M. Winslow ◽  
V.J. Twombly ◽  
M.P. Scott
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Maternal Effect ◽  
Positional Information ◽  
Drosophila Embryo ◽  
Dorsoventral Polarity ◽  
Anteroposterior Axis ◽  
Positional Marker ◽  
Control Pattern ◽  
The Relationship

At least 13 genes control the establishment of dorsoventral polarity in the Drosophila embryo and more than 30 genes control the anteroposterior pattern of body segments. Each group of genes is thought to control pattern formation along one body axis, independently of the other group. We have used the expression of the fushi tarazu (ftz) segmentation gene as a positional marker to investigate the relationship between the dorsoventral and anteroposterior axes. The ftz gene is normally expressed in seven transverse stripes. Changes in the striped pattern in embryos mutant for other genes (or progeny of females homozygous for maternal-effect mutations) can reveal alterations of cell fate resulting from such mutations. We show that in the absence of any of ten maternal-effect dorsoventral polarity gene functions, the characteristic stripes of ftz protein are altered. Normally there is a difference between ftz stripe spacing on the dorsal and ventral sides of the embryo; in dorsalized mutant embryos the ftz stripes appear to be altered so that dorsal-type spacing occurs on all sides of the embryo. These results indicate that cells respond to dorsoventral positional information in establishing early patterns of gene expression along the anteroposterior axis and that there may be more significant interactions between the different axes of positional information than previously determined.

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