Theory of mechanochemical patterning and optimal migration in cell monolayers

Boocock, Daniel; Hino, Naoko; Ružičková, Natália; Hirashima, Tsuyoshi; Hannezo, Édouard

doi:10.1038/s41567-020-01037-7

Cited by 85 publications

(96 citation statements)

References 54 publications

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“…The ERK waves most often originated in outer cells (Figure 4H) which are mechanically linked through adherent junctions (Debnath et al, 2002). This potentially enables ERK activation through an EGFR mechanochemical crosstalk similar to the one already described above for collective migration (Aoki et al, 2017; Boocock et al, 2020; Hino et al, 2020). Consistently, ERK waves displayed a strong bias to propagate within the outer cell layer, and rarely propagated to inner cells (Figure 4I).…”

Section: Discussionmentioning

confidence: 77%

“…Recently, an EGFR-dependent, mechanochemical feedback loop has been identified in epithelial cell collectives. ERK pulse-triggered myosin-based contractility of a leader cell mechanically activates an ERK pulse in a follower cell to reactivate contractility (Aoki et al, 2017; Boocock et al, 2020; Hino et al, 2020). This leads to the emergence of a positive feedback in which ERK pulses drive contractility/motility, and at the same time can reactivate ERK pulses in adjacent cells, leading to ERK waves that can coordinate collective motility.…”

Section: Discussionmentioning

confidence: 99%

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Spatio-temporal Control of ERK Pulse Frequency Coordinates Fate Decisions during Mammary Acinar Morphogenesis

Ender

Gagliardi

Dobrzyński

et al. 2020

Preprint

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The signaling events controlling proliferation, survival, and apoptosis during mammary epithelial acinar morphogenesis remain poorly characterized. By imaging single-cell ERK activity dynamics in MCF10A acini, we find that these fates depend on the frequency of ERK pulses. High pulse frequency is observed during initial acinus growth, correlating with rapid cell motility. Subsequent decrease in motility correlates with lower ERK pulse frequency and quiescence. Later, during lumen formation, coordinated ERK waves emerge across multiple cells of an acinus, correlating with high and low ERK pulse frequency in outer surviving and inner dying cells respectively. A PIK3CA H1047R mutation, commonly observed in breast cancer, increases ERK pulse frequency and inner cell survival, causing loss of lumen formation. Optogenetic entrainment of ERK pulses causally connects high ERK pulse frequency with inner cell survival. Thus, fate decisions during acinar morphogenesis are fine-tuned by different spatio-temporal coordination modalities of ERK pulse frequency.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Spatio-temporal Control of ERK Pulse Frequency Coordinates Fate Decisions during Mammary Acinar Morphogenesis

Ender

Gagliardi

Dobrzyński

et al. 2020

Preprint

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“…The cross-correlation analysis and ERK inactivation assay suggested a regulatory regime of coupling between the ERK activation and cell migration; the extension-triggered ERK activation promotes cell contraction and pulling the neighboring cells, which eventually evokes transmission of ERK activation to the neighboring cells, that is, mechanochemical feedback ( Boocock et al, 2021 ; Hino et al, 2020 ). To further verify this regime underlying the developing cochlear duct, we first suppressed actomyosin cell contraction by treating the E12.5 cochlea with blebbistatin.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, we and others have observed intercellular ERK activation waves in the epithelium, such as migrating Madin–Darby canine kidney (MDCK) cells ( Aoki et al, 2017 ; Hino et al, 2020 ), developing Drosophila tracheal placode ( Ogura et al, 2018 ), and wounded murine skin ( Hiratsuka et al, 2015 ). We have also proposed an ERK-mediated mechanochemical feedback system, in which cell extension activates ERK followed by ERK-triggered cell contraction ( Boocock et al, 2021 ; Hino et al, 2020 ) that can explain the coordination between cell movement and ERK activity. The ERK activation wave speed in the developing cochlear duct was 0.42 µm min −1 ( Figure 3F ), which is slower than in MDCK cells and wounded mouse epidermis, where it proceeds at 2.5 µm min −1 and 1.4 µm min −1 , respectively ( Aoki et al, 2017 ; Hino et al, 2020 ; Hiratsuka et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis

Ishii

Tateya

Matsuda

et al. 2021

eLife

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A notable example of spiral architecture in organs is the mammalian cochlear duct, where the morphology is critical for hearing function. Genetic studies have revealed necessary signaling molecules, but it remains unclear how cellular dynamics generate elongating, bending, and coiling of the cochlear duct. Here, we show that extracellular signal-regulated kinase (ERK) activation waves control collective cell migration during the murine cochlear duct development using deep tissue live-cell imaging, Förster resonance energy transfer (FRET)-based quantitation, and mathematical modeling. Long-term FRET imaging reveals that helical ERK activation propagates from the apex duct tip concomitant with the reverse multicellular flow on the lateral side of the developing cochlear duct, resulting in advection-based duct elongation. Moreover, model simulations, together with experiments, explain that the oscillatory wave trains of ERK activity and the cell flow are generated by mechanochemical feedback. Our findings propose a regulatory mechanism to coordinate the multicellular behaviors underlying the duct elongation during development.

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“…This positive feedback loop between mechanical forces and Erk activation (24) can result in traveling waves. It has been proposed that the coupling of forces and Erk activity facilitates long-range order and migration in the direction of the wound (31), whereas mechanical forces alone would tend to lose directionality and strength while spreading across a tissue (32, 33).…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of Erk activity waves in regenerating zebrafish scales

Hayden

Poss

Simone

et al. 2021

Preprint

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Erk signaling regulates cellular decisions in many biological contexts. Recently, we have reported a series of Erk activity traveling waves that coordinate regeneration of osteoblast tissue in zebrafish scales. These waves originate from a central source region, propagate as expanding rings, and impart cell growth, thus controlling tissue morphogenesis. Here, we present a minimal reaction-diffusion model for Erk activity waves. The model considers three components: Erk, a diffusible Erk-activator, and an Erk-inhibitor. Erk stimulates both its activator and inhibitor, forming a positive and negative feedback loop, respectively. Our model shows that this system can be excitable and propagate Erk activity waves. Waves originate from a pulsatile source which is modeled by adding a localized basal production of the activator that switches the source region from an excitable to an oscillatory state. As Erk activity periodically rises in the source, it can trigger an excitable wave which travels across the entire tissue. Analysis of the model finds that positive feedback controls the properties of the traveling wavefront and that negative feedback controls the duration of Erk activity peak and the period of Erk activity waves. The geometrical properties of the waves facilitate constraints on the effective diffusivity of the activator, indicating that waves are an efficient mechanism to transfer growth factor signaling rapidly across a large tissue.Significance statementSignaling waves represent a possible mechanism of spatiotemporal organization of multicellular tissues. We have recently shown that waves of activity of the kinase Erk control osteoblast regeneration in adult zebrafish scales. Here, we present a detailed characterization of a mathematical model of these signaling waves. We show that a source region poised in an oscillatory state can broadcast traveling waves of Erk activity in the surrounding excitable tissue. The dynamics of the source control the number and frequency of waves. Geometrical arguments support the notion that excitable Erk waves are an effective mechanism to transport growth factor signaling across a large regenerating tissue.

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Theory of mechanochemical patterning and optimal migration in cell monolayers

Cited by 85 publications

References 54 publications

Spatio-temporal Control of ERK Pulse Frequency Coordinates Fate Decisions during Mammary Acinar Morphogenesis

Spatio-temporal Control of ERK Pulse Frequency Coordinates Fate Decisions during Mammary Acinar Morphogenesis

Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis

Mathematical modeling of Erk activity waves in regenerating zebrafish scales

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