Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

Ambrosi, Priscilla; Chahda, Juan Sebastian; Koslen, Hannah R.; Chiel, Hillel J.; Mizutani, Claudia Mieko

doi:10.1371/journal.pcbi.1003807

Cited by 22 publications

(38 citation statements)

References 43 publications

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“…This model also proved extremely powerful when comparing nDl gradient formation in related drosophilids. (Ambrosi et al, 2014). In this publication, Ambrosi also suggest that Cactus is the most important element that allows the correct gradient accommodation in embryos of greatly divergent sizes.…”

Section: Two Routes For Dorsal Nuclear Translocation As An Extension mentioning

confidence: 84%

A Reaction-Diffusion Network model predicts a dual role of Cactus/IκB to regulate Dorsal/NFκB nuclear translocation inDrosophila

Barros

Cardoso

Bisch

et al. 2020

Preprint

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Dorsal-ventral patterning of the Drosophila embryo depends on the NFκB superfamily transcription factor Dorsal (Dl). Toll receptor activation signals for degradation of the IκB inhibitor Cactus (Cact), leading to a ventral-to-dorsal nuclear Dl gradient. Cact is critical for Dl nuclear import, as it binds to and prevents Dl from entering the nuclei. Quantitative analysis of cact mutants revealed an additional Cact function to promote Dl nuclear translocation in ventral regions of the embryo. To investigate this dual Cact role, we developed a predictive model based on a reaction-diffusion regulatory network. This network considers non-uniform Toll activation as well as Toll-dependent Dl nuclear import and Cact degradation. In addition, it incorporates translational control of Cact levels by Dl, a Toll-independent pathway for Cact regulation and reversible nuclear-cytoplasmic Dl flow. Our model successfully reproduces wild-type data and emulates the Dl nuclear gradient in mutant dl and cact allelic combinations. Our results indicate that the dual role of Cact depends on targeting distinct Dl complexes along the dorsal-ventral axis: In the absence of Toll activation, free Dl-Cact trimers inhibit direct Dl nuclear entry; upon ventral-lateral Toll activation, Dl-Cact trimers are recruited into predominant signaling complexes and promote active Dl nuclear translocation. Simulations suggest that Toll-independent regulatory mechanisms that target Cact are fundamental to reproduce the full assortment of Cact effects. Considering the high evolutionary conservation of these pathways, our analysis should contribute to understand NFκB/c-Rel activation in other contexts such as in the vertebrate immune system and disease.

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Section: Two Routes For Dorsal Nuclear Translocation As An Extension mentioning

confidence: 84%

A Reaction-Diffusion Network model predicts a dual role of Cactus/IκB to regulate Dorsal/NFκB nuclear translocation inDrosophila

Barros

Cardoso

Bisch

et al. 2020

Preprint

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“…In addition to reduced diffusivity resulting in a hallmark shuttling phenotypes, it was also shown that embryos from heterozygous dl null mothers exhibited the hallmark phenotypes to varying degrees (Fig. 2C) [6,17,32]. However, no previous model of the Dl gradient, including our initial models, could reproduce this phenotype when lowering only the dosage of Dl [17,[32][33][34].…”

Section: Evidence Of Shuttling In the Dorsal Gradientmentioning

confidence: 85%

“…Any system with these four features, balanced in the proper way, may exhibit shuttling. Indeed, previous models of the Dl/Cact system, which captured these four features, exhibited shuttling without the express intention of the modelers [32].…”

Section: Evidence Of Shuttling In the Dorsal Gradientmentioning

confidence: 99%

Shuttling of Dorsal by Cactus: mechanism and implications

Schloop

Carrell-Noel

Reeves

2019

Preprint

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In a developing animal, morphogen gradients act to pattern tissues into distinct domains of cell types. However, despite their prevalence in development, morphogen gradient formation is a matter of debate. In our recent publication, we showed that the Dorsal/NF-κB morphogen gradient, which patterns the DV axis of the early Drosophila embryo, is partially established by a mechanism of facilitated diffusion. This mechanism, also known as "shuttling," occurs when a binding partner of the morphogen facilitates the diffusion of the morphogen, allowing it to accumulate at a given site. In this case, the inhibitor Cactus/IκB facilitates the diffusion of Dorsal/NF-κB. In the fly embryo, we used computation and experiment to not only show that shuttling occurs in the embryo, but also that it enables the viability of embryos that inherit only one copy of dorsal maternally. Here we further discuss our evidence behind the shuttling mechanism, the previous literature data explained by the mechanism, and how it may also be critical for robustness of development. Finally, we describe an interaction between Dorsal and BMP signaling that is likely affected by shuttling.

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“…Hence, interplay between Toll signaling and the embryo morphology may regulate scaling of the Dorsal gradient function (Ambrosi et al . ). On the dorsal side of the embryo, Dpp (a member of the BMP family) also forms a robust concentration gradient that scales to embryo size (Eldar et al .…”

Section: Scaling Of Gene Expression Boundaries In the Early Drosophilmentioning

confidence: 97%

“…Cross-species analysis of Dorsal activity identified that the threshold response to Dorsal concentration remained relatively stable, but (downstream) Toll activation was highly variable (Chahda et al 2013). Hence, interplay between Toll signaling and the embryo morphology may regulate scaling of the Dorsal gradient function (Ambrosi et al 2014). On the dorsal side of the embryo, Dpp (a member of the BMP family) also forms a robust concentration gradient that scales to embryo size (Eldar et al 2002;Mizutani et al 2005).…”

Section: Scaling Of Gene Expression Boundaries Along the Dorsal-ventrmentioning

confidence: 99%

Gene expression boundary scaling and organ size regulation in the Drosophila embryo

Amourda

Saunders

2017

Dev Growth Differ

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How the shape and size of tissues and organs is regulated during development is a major question in developmental biology. Such regulation relies upon both intrinsic cues (such as signaling networks) and extrinsic inputs (such as from neighboring tissues). Here, we focus on pattern formation and organ development during Drosophila embryogenesis. In particular, we outline the importance of both biochemical and mechanical tissue-tissue interactions in size regulation. We describe how the Drosophila embryo can potentially provide novel insights into how shape and size are regulated during development. We focus on gene expression boundary scaling in the early embryo and how size is regulated in three organs (hindgut, trachea, and ventral nerve cord) later in development, with particular focus on the role of tissue-tissue interactions. Overall, we demonstrate that Drosophila embryogenesis provides a suitable model system for studying spatial and temporal scaling and size control in vivo.

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Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

Cited by 22 publications

References 43 publications

A Reaction-Diffusion Network model predicts a dual role of Cactus/IκB to regulate Dorsal/NFκB nuclear translocation inDrosophila

A Reaction-Diffusion Network model predicts a dual role of Cactus/IκB to regulate Dorsal/NFκB nuclear translocation inDrosophila

Shuttling of Dorsal by Cactus: mechanism and implications

Gene expression boundary scaling and organ size regulation in the Drosophila embryo

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