ERK signaling dissolves ERF repression condensates in living embryos

Weaver, Claire J.; Patel, Aleena L.; Shvartsman, Stanislav Y.; Levine, Michael; Treen, Nicholas

doi:10.1073/pnas.2119187119

Cited by 10 publications

(14 citation statements)

References 38 publications

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“…the relation between the fraction of phosphorylated activator, A p and active ERK, Erk � . Lower panel: Heatmaps showing the Hill coefficients of the relation between Otx and Erk � when changing the values of the k MMi in Eqs (16)(17). (E) Relation between the level of Otx expression predicted by the model (O) and cell surface in contact with FGF-expressing mesendoderm cells (S 1 ) in the presence (blue curve, Hill coefficient = 14.2) or in the absence (orange curve, Hill coefficient = 5.7) of the repressor I.…”

Section: Plos Computational Biologymentioning

confidence: 99%

“…To obtain an expression for Otx expression (O and Otx smFISH ) as a function of the inputs of the signaling cascade (S 1 ) we combined the models of ERK activity and of Otx expression presented in the previous sections. We computed ERK activity using Eq (1) and we used this as the input (Erk � ) to compute the fraction of active Ets1/2 (A p ) and active ERF2 (I) using Eqs ( 16) and (17). Then we computed the level of Otx expression by solving Eq (15).…”

Section: Model Of Otx Expressionmentioning

confidence: 99%

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Model of neural induction in the ascidian embryo

et al. 2023

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How cell specification can be controlled in a reproducible manner is a fundamental question in developmental biology. In ascidians, a group of invertebrate chordates, geometry plays a key role in achieving this control. Here, we use mathematical modeling to demonstrate that geometry dictates the neural-epidermal cell fate choice in the 32-cell stage ascidian embryo by a two-step process involving first the modulation of ERK signaling and second, the expression of the neural marker gene, Otx. The model describes signal transduction by the ERK pathway that is stimulated by FGF and attenuated by ephrin, and ERK-mediated control of Otx gene expression, which involves both an activator and a repressor of ETS-family transcription factors. Considering the measured area of cell surface contacts with FGF- or ephrin-expressing cells as inputs, the solutions of the model reproduce the experimental observations about ERK activation and Otx expression in the different cells under normal and perturbed conditions. Sensitivity analyses and computations of Hill coefficients allow us to quantify the robustness of the specification mechanism controlled by cell surface area and to identify the respective role played by each signaling input. Simulations also predict in which conditions the dual control of gene expression by an activator and a repressor that are both under the control of ERK can induce a robust ON/OFF control of neural fate induction.

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Section: Plos Computational Biologymentioning

confidence: 99%

Section: Model Of Otx Expressionmentioning

confidence: 99%

Model of neural induction in the ascidian embryo

et al. 2023

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“…In contrast, the transcription of the immediate-early gene Otx is bimodal, with a ON response that is restricted to neural precursors. We hypothesized that the ON/OFF response is, at least in part, due to the dual control of Otx expression (Williaume et al, 2021): ETS1/2 phosphorylation by ERK is required for its transcriptional activator activity (Weaver et al, 2022), while phosphorylation of the ERF2 repressor by dpERK promotes its nuclear export, thus preventing its binding to DNA (Le Gallic et al, 1999;2004) (Fig. 1A).…”

Section: Dual Control Of the Expression Of The Otx Gene By Erkmentioning

confidence: 99%

“…The Ets2 repressor factor 2 (ERF2) (Yagi et al, 2003) recognizes the same binding site as the transcriptional activator ETS1/2 and its activity is negatively controlled by ERK via nuclear export (Le Gallic et al, 1999;2004;and Weaver et al, 2022). Thus, we considered that Otx expression is enhanced by the stimulation of an activator (A; e.g.…”

Section: Model Of Otx Expressionmentioning

confidence: 99%

Model of neural induction in the ascidian embryo

Bettoni

Hudson

Yasuo

et al. 2022

Preprint

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How cell specification can be controlled in a reproducible manner is a fundamental question in development biology. In ascidians, a group of marine invertebrate chordates, geometry plays a key role in achieving this control. Here, we use mathematical modeling to demonstrate that geometry dictates the neural-epidermal cell fate choice in the 32-cell stage ascidian embryo by a two-step process involving first the modulation of ERK signaling and second, the expression of the neural marker gene, Otx. The model describes signal transduction by the ERK pathway that is stimulated by FGF and repressed by ephrin, and ERK-mediated control of Otx gene expression, which involves both an activator and an inhibitor of transcription. Considering the measured area of cell surface contacts with FGF- or ephrin-expressing cells as inputs, the solutions of the model reproduce the experimental observations about ERK activation and Otx expression in the different cells under normal and perturbed conditions. Sensitivity analyses and computations of Hill coefficients allow to quantify the robustness of the specification mechanism controlled by cell surface area and to identify the respective role played by each signaling input. Simulations also predict in which conditions the dual control of gene expression by an activator and an inhibitor that are both under the control of ERK can induce a robust ON/OFF control of neural fate induction

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“…ERF was also shown to repress Otx in Ciona embryos at the 32-cell stage (Williaume et al 2021). Interestingly, we previously observed that ERF condensates were able to dissolve and reform within a single interphase (Weaver et al 2022), suggesting a dynamic response to endogenous FGF signals.…”

Section: Introductionmentioning

confidence: 99%

An FGF Timer for Zygotic Genome Activation

Treen

Chavarria

Weaver

et al. 2022

Preprint

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Zygotic genome activation has been extensively studied in a variety of systems including flies, frogs, and mammals. However, there is comparatively little known about the precise timings of gene induction during the earliest phases of embryogenesis. Here we employ high-resolution in situ detection methods, along with genetic and experimental manipulations, to study the timing of zygotic activation in the simple model chordate, Ciona intestinalis with minute-scale temporal precision. We found that two Prdm1 homologs in Ciona are the earliest genes that respond to FGF signaling. We present evidence for a FGF timing mechanism that is driven by derepression of the ERF repressor by ERK activity, which works in concert with localized activators such as Foxa.a. Absence of ERF results in derepression of target genes throughout the embryo. A highlight of this timer is the sharp transition in FGF responsiveness between the 8- and 16-cell stages of development. We propose that this timer is an innovation of chordates that is also employed by other vertebrates.

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ERK signaling dissolves ERF repression condensates in living embryos

Cited by 10 publications

References 38 publications

Model of neural induction in the ascidian embryo

Model of neural induction in the ascidian embryo

Model of neural induction in the ascidian embryo

An FGF Timer for Zygotic Genome Activation

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