Feedback inhibition of actin on Rho mediates content release from large secretory vesicles

Segal, Dagan; Zaritsky, Assaf; Schejter, Eyal D.; Shilo, Ben‐Zion

doi:10.1083/jcb.201711006

Cited by 48 publications

(80 citation statements)

References 43 publications

(64 reference statements)

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“…The apicosome-like structures observed in E3.25 embryos ( Figure 2C) show that ICM cells isolated from contact-free surfaces can generate luminal precursor-like structures (Taniguchi et al, 2015 and, which is in line with the observation that all cells of the embryo contribute to lumen formation. Furthermore, the morphology and secretion dynamics of the vesicles reported here are markedly similar to those present in systems that require regulated secretion of contents from large vesicles into a lumen (Miklavc et al, 2012;Rousso et al, 2016;Segal et al, 2018;Tran et al, 2015). If molecules such as morphogens or chemokines are secreted through this mechanism there could be a causal link between fluid accumulation and fate specification and/or cell migration (Durdu et al, 2014).…”

Section: Discussionsupporting

confidence: 67%

Lumen expansion facilitates epiblast-primitive endoderm fate specification in the mouse blastocyst formation

Ryan

Chan²,

Graner

et al. 2019

Preprint

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Mouse blastocyst formation involves lumen formation and cell fate specification. While many studies have investigated how the blastocyst cell lineages are specified through genetics and signaling, studies into the potential role of the fluid lumen have yet to be conducted. We discover that blastocyst fluid emerges by secretion of cytoplasmic vesicles to intercellular space in addition to trans-epithelial flow. We observe that the beginning of epiblast and primitive endoderm spatial segregation directly follows lumen coalescence. Notably, we show that perturbing lumen expansion by pharmacological and biophysical means impair the specification and spatial segregation of primitive endoderm cells within the blastocyst. Combined, our results suggest that blastocyst lumen expansion plays a critical role in guiding cell fate specification and positioning. As epithelial tissues typically form lumina, lumen expansion may provide a general mechanism of cell fate control in many tissues.

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Section: Discussionsupporting

confidence: 67%

Lumen expansion facilitates epiblast-primitive endoderm fate specification in the mouse blastocyst formation

Ryan

Chan²,

Graner

et al. 2019

Preprint

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“…The mechanism(s) by which F-actin feeds back to inactivate RhoA in these cells remains unknown, but our observations in C. elegans support to the idea, proposed by Bement et al, 2015, that a RhoGAP homologous (or analogous) to RGA-3/4 may be recruited by F-actin to mediate negative feedback in frog and echinoderm cells. A similar mechanism has recently been reported in the context of secreting in Drosophila larval salivary glands (Segal et al, 2018), and a similar circuit design may underlie the propagation of actin waves observed in many motile cells (reviewed in (Allard and Mogilner, 2013)).…”

Section: Discussionsupporting

confidence: 59%

Excitable RhoA dynamics drive pulsed contractions in the earlyC. elegansembryo

Robin

McFadden

Munro

2016

Preprint

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Pulsed actomyosin contractility underlies diverse modes of tissue morphogenesis, but the underlying mechanisms remain poorly understood. Here, we combine quantitative imaging with genetic perturbations to identify a core mechanism for pulsed contractility in early C. elegans embryos. We show that pulsed accumulation of actomyosin is governed by local control of assembly and disassembly downstream of RhoA. Pulsed activation and inactivation of RhoA precede, respectively, accumulation and disappearance of actomyosin, and persist in the nearly complete absence of Myosin II.We find that fast positive feedback on RhoA activation drives pulse initiation, while Factin dependent accumulation of the RhoA GTPase activating proteins (GAPs) RGA-3/4 provides delayed negative feedback to terminate each pulse. An experimentally constrained mathematical model confirms that in principle these feedbacks are sufficient to generate locally excitable RhoA dynamics. We propose that excitable RhoA dynamics are a common driver for pulsed contractility that can be differently tuned or coupled to actomyosin dynamics to produce a diversity of morphogenetic outcomes.

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“…Furthermore, we assume negative Hill-type F-actin feedback on ANP activation. This introduces the previously reported negative feedback of F-Actin on the activity of Rho-GTPases (Bement et al, 2015;Michaux et al, 2018;Segal et al, 2018). Notably, in our simulations we found this feedback to increase the number of parameter combinations that produce oscillatory dynamics suggesting that this feedback merely serves to provide additional robustness (Appendix Supplementary Methods).…”

Section: Fe Modelling Of F-actin Dynamics In As Cellssupporting

confidence: 80%

Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis

Atzeni

Pasakarnis

Mosca

et al. 2020

Preprint

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Tissue morphogenesis integrates cell type-specific biochemistry and architecture, cellular force generation and mechanisms coordinating forces amongst neighbouring cells and tissues.We use finite element-based modelling to explore the interconnections at these multiple biological scales in embryonic dorsal closure, where pulsed actomyosin contractility in adjacent Amnioserosa (AS) cells powers the closure of an epidermis opening. Based on our in vivo observations, the model implements F-actin nucleation periodicity that is independent of MyoII activity. Our model reveals conditions, where depleting MyoII activity nevertheless indirectly affects oscillatory F-actin behaviour, without the need for biochemical feedback. In addition, it questions the previously proposed role of Dpp-mediated regulation of the patterned actomyosin dynamics in the AS tissue, suggesting them to be emergent. Tissue-specific Dpp interference supports the model's prediction. The model further predicts that the mechanical properties of the surrounding epidermis tissue feed back on the shaping and patterning of the AS tissue. Finally, our model's parameter space reproduces mutant phenotypes and provides predictions for their underlying cause. Our modelling approach thus reveals several unappreciated mechanistic properties of tissue morphogenesis.

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Feedback inhibition of actin on Rho mediates content release from large secretory vesicles

Cited by 48 publications

References 43 publications

Lumen expansion facilitates epiblast-primitive endoderm fate specification in the mouse blastocyst formation

Lumen expansion facilitates epiblast-primitive endoderm fate specification in the mouse blastocyst formation

Excitable RhoA dynamics drive pulsed contractions in the earlyC. elegansembryo

Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis

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