Cells

Editorial

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4 pages, 195 KiB

Open AccessEditorial

Symmetry Breaking as an Interdisciplinary Concept Unifying Cell and Developmental Biology

by Andrew B. Goryachev

Cells 2021, 10(1), 86; https://doi.org/10.3390/cells10010086 - 7 Jan 2021

Cited by 1 | Viewed by 2716

Abstract

The concept of “symmetry breaking” has become a mainstay of modern biology, yet you will not find a definition of this concept specific to biological systems in Wikipedia [...] Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

Research

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20 pages, 2493 KiB

Open AccessArticle

Activation of Cdc42 GTPase upon CRY2-Induced Cortical Recruitment Is Antagonized by GAPs in Fission Yeast

by Iker Lamas, Nathalie Weber and Sophie G. Martin

Cells 2020, 9(9), 2089; https://doi.org/10.3390/cells9092089 - 12 Sep 2020

Cited by 9 | Viewed by 4064

Abstract

The small GTPase Cdc42 is critical for cell polarization in eukaryotic cells. In rod-shaped fission yeast Schizosaccharomyces pombe cells, active GTP-bound Cdc42 promotes polarized growth at cell poles, while inactive Cdc42-GDP localizes ubiquitously also along cell sides. Zones of Cdc42 activity are maintained [...] Read more.

The small GTPase Cdc42 is critical for cell polarization in eukaryotic cells. In rod-shaped fission yeast Schizosaccharomyces pombe cells, active GTP-bound Cdc42 promotes polarized growth at cell poles, while inactive Cdc42-GDP localizes ubiquitously also along cell sides. Zones of Cdc42 activity are maintained by positive feedback amplification involving the formation of a complex between Cdc42-GTP, the scaffold Scd2, and the guanine nucleotide exchange factor (GEF) Scd1, which promotes the activation of more Cdc42. Here, we use the CRY2-CIB1 optogenetic system to recruit and cluster a cytosolic Cdc42 variant at the plasma membrane and show that this leads to its moderate activation also on cell sides. Surprisingly, Scd2, which binds Cdc42-GTP, is still recruited to CRY2-Cdc42 clusters at cell sides in individual deletion of the GEFs Scd1 or Gef1. We show that activated Cdc42 clusters at cell sides are able to recruit Scd1, dependent on the scaffold Scd2. However, Cdc42 activity is not amplified by positive feedback and does not lead to morphogenetic changes, due to antagonistic activity of the GTPase activating protein Rga4. Thus, the cell architecture is robust to moderate activation of Cdc42 at cell sides. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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23 pages, 1312 KiB

Open AccessArticle

CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization

by Sungrim Seirin-Lee, Eamonn A. Gaffney and Adriana T. Dawes

Cells 2020, 9(9), 2036; https://doi.org/10.3390/cells9092036 - 5 Sep 2020

Cited by 9 | Viewed by 3244

Abstract

Many cells rearrange proteins and other components into spatially distinct domains in a process called polarization. This asymmetric patterning is required for a number of biological processes including asymmetric division, cell migration, and embryonic development. Proteins involved in polarization are highly conserved and [...] Read more.

Many cells rearrange proteins and other components into spatially distinct domains in a process called polarization. This asymmetric patterning is required for a number of biological processes including asymmetric division, cell migration, and embryonic development. Proteins involved in polarization are highly conserved and include members of the Par and Rho protein families. Despite the importance of these proteins in polarization, it is not yet known how they interact and regulate each other to produce the protein localization patterns associated with polarization. In this study, we develop and analyse a biologically based mathematical model of polarization that incorporates interactions between Par and Rho proteins that are consistent with experimental observations of CDC-42. Using minimal network and eFAST sensitivity analyses, we demonstrate that CDC-42 is predicted to reinforce maintenance of anterior PAR protein polarity which in turn feedbacks to maintain CDC-42 polarization, as well as supporting posterior PAR protein polarization maintenance. The mechanisms for polarity maintenance identified by these methods are not sufficient for the generation of polarization in the absence of cortical flow. Additional inhibitory interactions mediated by the posterior Par proteins are predicted to play a role in the generation of Par protein polarity. More generally, these results provide new insights into the role of CDC-42 in polarization and the mutual regulation of key polarity determinants, in addition to providing a foundation for further investigations. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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16 pages, 6307 KiB

Open AccessArticle

Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition

by Bita Khalili, Hailey D. Lovelace, David M. Rutkowski, Danielle Holz and Dimitrios Vavylonis

Cells 2020, 9(8), 1769; https://doi.org/10.3390/cells9081769 - 24 Jul 2020

Cited by 9 | Viewed by 3776

Abstract

Cells polarize for growth, motion, or mating through regulation of membrane-bound small GTPases between active GTP-bound and inactive GDP-bound forms. Activators (GEFs, GTP exchange factors) and inhibitors (GAPs, GTPase activating proteins) provide positive and negative feedbacks. We show that a reaction–diffusion model on [...] Read more.

Cells polarize for growth, motion, or mating through regulation of membrane-bound small GTPases between active GTP-bound and inactive GDP-bound forms. Activators (GEFs, GTP exchange factors) and inhibitors (GAPs, GTPase activating proteins) provide positive and negative feedbacks. We show that a reaction–diffusion model on a curved surface accounts for key features of polarization of model organism fission yeast. The model implements Cdc42 membrane diffusion using measured values for diffusion coefficients and dissociation rates and assumes a limiting GEF pool (proteins Gef1 and Scd1), as in prior models for budding yeast. The model includes two types of GAPs, one representing tip-localized GAPs, such as Rga3; and one representing side-localized GAPs, such as Rga4 and Rga6, that we assume switch between fast and slow diffusing states. After adjustment of unknown rate constants, the model reproduces active Cdc42 zones at cell tips and the pattern of GEF and GAP localization at cell tips and sides. The model reproduces observed tip-to-tip oscillations with periods of the order of several minutes, as well as asymmetric to symmetric oscillations transitions (corresponding to NETO “new end take off”), assuming the limiting GEF amount increases with cell size. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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19 pages, 3299 KiB

Open AccessArticle

Flow Induced Symmetry Breaking in a Conceptual Polarity Model

by Manon C. Wigbers, Fridtjof Brauns, Ching Yee Leung and Erwin Frey

Cells 2020, 9(6), 1524; https://doi.org/10.3390/cells9061524 - 23 Jun 2020

Cited by 8 | Viewed by 3325

Abstract

Important cellular processes, such as cell motility and cell division, are coordinated by cell polarity, which is determined by the non-uniform distribution of certain proteins. Such protein patterns form via an interplay of protein reactions and protein transport. Since Turing’s seminal work, the [...] Read more.

Important cellular processes, such as cell motility and cell division, are coordinated by cell polarity, which is determined by the non-uniform distribution of certain proteins. Such protein patterns form via an interplay of protein reactions and protein transport. Since Turing’s seminal work, the formation of protein patterns resulting from the interplay between reactions and diffusive transport has been widely studied. Over the last few years, increasing evidence shows that also advective transport, resulting from cytosolic and cortical flows, is present in many cells. However, it remains unclear how and whether these flows contribute to protein-pattern formation. To address this question, we use a minimal model that conserves the total protein mass to characterize the effects of cytosolic flow on pattern formation. Combining a linear stability analysis with numerical simulations, we find that membrane-bound protein patterns propagate against the direction of cytoplasmic flow with a speed that is maximal for intermediate flow speed. We show that the mechanism underlying this pattern propagation relies on a higher protein influx on the upstream side of the pattern compared to the downstream side. Furthermore, we find that cytosolic flow can change the membrane pattern qualitatively from a peak pattern to a mesa pattern. Finally, our study shows that a non-uniform flow profile can induce pattern formation by triggering a regional lateral instability. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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18 pages, 6521 KiB

Open AccessCommunication

Unilateral Cleavage Furrows in Multinucleate Cells

by Julia Bindl, Eszter Sarolta Molnar, Mary Ecke, Jana Prassler, Annette Müller-Taubenberger and Günther Gerisch

Cells 2020, 9(6), 1493; https://doi.org/10.3390/cells9061493 - 18 Jun 2020

Cited by 9 | Viewed by 3568

Abstract

Multinucleate cells can be produced in Dictyostelium by electric pulse-induced fusion. In these cells, unilateral cleavage furrows are formed at spaces between areas that are controlled by aster microtubules. A peculiarity of unilateral cleavage furrows is their propensity to join laterally with other [...] Read more.

Multinucleate cells can be produced in Dictyostelium by electric pulse-induced fusion. In these cells, unilateral cleavage furrows are formed at spaces between areas that are controlled by aster microtubules. A peculiarity of unilateral cleavage furrows is their propensity to join laterally with other furrows into rings to form constrictions. This means cytokinesis is biphasic in multinucleate cells, the final abscission of daughter cells being independent of the initial direction of furrow progression. Myosin-II and the actin filament cross-linking protein cortexillin accumulate in unilateral furrows, as they do in the normal cleavage furrows of mononucleate cells. In a myosin-II-null background, multinucleate or mononucleate cells were produced by cultivation either in suspension or on an adhesive substrate. Myosin-II is not essential for cytokinesis either in mononucleate or in multinucleate cells but stabilizes and confines the position of the cleavage furrows. In fused wild-type cells, unilateral furrows ingress with an average velocity of 1.7 µm × min⁻¹, with no appreciable decrease of velocity in the course of ingression. In multinucleate myosin-II-null cells, some of the furrows stop growing, thus leaving space for the extensive broadening of the few remaining furrows. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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10 pages, 1598 KiB

Open AccessArticle

Symmetry Breaking and Emergence of Directional Flows in Minimal Actomyosin Cortices

by Sven K. Vogel, Christian Wölfer, Diego A. Ramirez-Diaz, Robert J. Flassig, Kai Sundmacher and Petra Schwille

Cells 2020, 9(6), 1432; https://doi.org/10.3390/cells9061432 - 9 Jun 2020

Cited by 8 | Viewed by 3407

Abstract

Cortical actomyosin flows, among other mechanisms, scale up spontaneous symmetry breaking and thus play pivotal roles in cell differentiation, division, and motility. According to many model systems, myosin motor-induced local contractions of initially isotropic actomyosin cortices are nucleation points for generating cortical flows. [...] Read more.

Cortical actomyosin flows, among other mechanisms, scale up spontaneous symmetry breaking and thus play pivotal roles in cell differentiation, division, and motility. According to many model systems, myosin motor-induced local contractions of initially isotropic actomyosin cortices are nucleation points for generating cortical flows. However, the positive feedback mechanisms by which spontaneous contractions can be amplified towards large-scale directed flows remain mostly speculative. To investigate such a process on spherical surfaces, we reconstituted and confined initially isotropic minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced local contractions that self-organize and amplify into directed large-scale actomyosin flows. By combining our experiments with theory, we found that the feedback mechanism leading to a coordinated directional motion of actomyosin clusters can be described as asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption with spatial confinement. We identified fingerprints of vibrational states as the basis of directed motions by tracking individual actomyosin clusters. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinement in vitro and in living systems. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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18 pages, 12559 KiB

Open AccessArticle

Cell-Substrate Patterns Driven by Curvature-Sensitive Actin Polymerization: Waves and Podosomes

by Moshe Naoz and Nir S. Gov

Cells 2020, 9(3), 782; https://doi.org/10.3390/cells9030782 - 23 Mar 2020

Cited by 5 | Viewed by 4002

Abstract

Cells adhered to an external solid substrate are observed to exhibit rich dynamics of actin structures on the basal membrane, which are distinct from those observed on the dorsal (free) membrane. Here we explore the dynamics of curved membrane proteins, or protein complexes, [...] Read more.

Cells adhered to an external solid substrate are observed to exhibit rich dynamics of actin structures on the basal membrane, which are distinct from those observed on the dorsal (free) membrane. Here we explore the dynamics of curved membrane proteins, or protein complexes, that recruit actin polymerization when the membrane is confined by the solid substrate. Such curved proteins can induce the spontaneous formation of membrane protrusions on the dorsal side of cells. However, on the basal side of the cells, such protrusions can only extend as far as the solid substrate and this constraint can convert such protrusions into propagating wave-like structures. We also demonstrate that adhesion molecules can stabilize localized protrusions that resemble some features of podosomes. This coupling of curvature and actin forces may underlie the differences in the observed actin-membrane dynamics between the basal and dorsal sides of adhered cells. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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Review

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26 pages, 2112 KiB

Open AccessReview

The Path towards Predicting Evolution as Illustrated in Yeast Cell Polarity

by Werner Karl-Gustav Daalman, Els Sweep and Liedewij Laan

Cells 2020, 9(12), 2534; https://doi.org/10.3390/cells9122534 - 24 Nov 2020

Cited by 2 | Viewed by 4523

Abstract

A bottom-up route towards predicting evolution relies on a deep understanding of the complex network that proteins form inside cells. In a rapidly expanding panorama of experimental possibilities, the most difficult question is how to conceptually approach the disentangling of such complex networks. [...] Read more.

A bottom-up route towards predicting evolution relies on a deep understanding of the complex network that proteins form inside cells. In a rapidly expanding panorama of experimental possibilities, the most difficult question is how to conceptually approach the disentangling of such complex networks. These can exhibit varying degrees of hierarchy and modularity, which obfuscate certain protein functions that may prove pivotal for adaptation. Using the well-established polarity network in budding yeast as a case study, we first organize current literature to highlight protein entrenchments inside polarity. Following three examples, we see how alternating between experimental novelties and subsequent emerging design strategies can construct a layered understanding, potent enough to reveal evolutionary targets. We show that if you want to understand a cell’s evolutionary capacity, such as possible future evolutionary paths, seemingly unimportant proteins need to be mapped and studied. Finally, we generalize this research structure to be applicable to other systems of interest. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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11 pages, 851 KiB

Open AccessReview

A “Numerical Evo-Devo” Synthesis for the Identification of Pattern-Forming Factors

by Richard Bailleul, Marie Manceau and Jonathan Touboul

Cells 2020, 9(8), 1840; https://doi.org/10.3390/cells9081840 - 5 Aug 2020

Cited by 5 | Viewed by 3339

Abstract

Animals display extensive diversity in motifs adorning their coat, yet these patterns have reproducible orientation and periodicity within species or groups. Morphological variation has been traditionally used to dissect the genetic basis of evolutionary change, while pattern conservation and stability in both mathematical [...] Read more.

Animals display extensive diversity in motifs adorning their coat, yet these patterns have reproducible orientation and periodicity within species or groups. Morphological variation has been traditionally used to dissect the genetic basis of evolutionary change, while pattern conservation and stability in both mathematical and organismal models has served to identify core developmental events. Two patterning theories, namely instruction and self-organisation, emerged from this work. Combined, they provide an appealing explanation for how natural patterns form and evolve, but in vivo factors underlying these mechanisms remain elusive. By bridging developmental biology and mathematics, novel frameworks recently allowed breakthroughs in our understanding of pattern establishment, unveiling how patterning strategies combine in space and time, or the importance of tissue morphogenesis in generating positional information. Adding results from surveys of natural variation to these empirical-modelling dialogues improves model inference, analysis, and in vivo testing. In this evo-devo-numerical synthesis, mathematical models have to reproduce not only given stable patterns but also the dynamics of their emergence, and the extent of inter-species variation in these dynamics through minimal parameter change. This integrative approach can help in disentangling molecular, cellular and mechanical interaction during pattern establishment. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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40 pages, 6131 KiB

Open AccessReview

The Roles of Signaling in Cytoskeletal Changes, Random Movement, Direction-Sensing and Polarization of Eukaryotic Cells

by Yougan Cheng, Bryan Felix and Hans G. Othmer

Cells 2020, 9(6), 1437; https://doi.org/10.3390/cells9061437 - 10 Jun 2020

Cited by 14 | Viewed by 4804

Abstract

Movement of cells and tissues is essential at various stages during the lifetime of an organism, including morphogenesis in early development, in the immune response to pathogens, and during wound-healing and tissue regeneration. Individual cells are able to move in a variety of [...] Read more.

Movement of cells and tissues is essential at various stages during the lifetime of an organism, including morphogenesis in early development, in the immune response to pathogens, and during wound-healing and tissue regeneration. Individual cells are able to move in a variety of microenvironments (MEs) (A glossary of the acronyms used herein is given at the end) by suitably adapting both their shape and how they transmit force to the ME, but how cells translate environmental signals into the forces that shape them and enable them to move is poorly understood. While many of the networks involved in signal detection, transduction and movement have been characterized, how intracellular signals control re-building of the cyctoskeleton to enable movement is not understood. In this review we discuss recent advances in our understanding of signal transduction networks related to direction-sensing and movement, and some of the problems that remain to be solved. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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12 pages, 1016 KiB

Open AccessReview

Symmetry Breaking and Epithelial Cell Extrusion

by Bageshri Naimish Nanavati, Alpha S. Yap and Jessica L. Teo

Cells 2020, 9(6), 1416; https://doi.org/10.3390/cells9061416 - 7 Jun 2020

Cited by 11 | Viewed by 5660

Abstract

Cell extrusion is a striking morphological event found in epithelia and endothelia. It is distinguished by two symmetry-breaking events: a loss of planar symmetry, as cells are extruded in either apical or basal directions; and loss of mechanochemical homogeneity within monolayers, as cells [...] Read more.

Cell extrusion is a striking morphological event found in epithelia and endothelia. It is distinguished by two symmetry-breaking events: a loss of planar symmetry, as cells are extruded in either apical or basal directions; and loss of mechanochemical homogeneity within monolayers, as cells that are fated to be extruded become biochemically and mechanically distinct from their neighbors. Cell extrusion is elicited by many diverse events, from apoptosis to the expression of transforming oncogenes. Does the morphological outcome of extrusion reflect cellular processes that are common to these diverse biological phenomena? To address this question, in this review we compare the progress that has been made in understanding how extrusion is elicited by epithelial apoptosis and cell transformation. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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17 pages, 1959 KiB

Open AccessReview

Protein Phase Separation during Stress Adaptation and Cellular Memory

by Yasmin Lau, Henry Patrick Oamen and Fabrice Caudron

Cells 2020, 9(5), 1302; https://doi.org/10.3390/cells9051302 - 23 May 2020

Cited by 21 | Viewed by 6030

Abstract

Cells need to organise and regulate their biochemical processes both in space and time in order to adapt to their surrounding environment. Spatial organisation of cellular components is facilitated by a complex network of membrane bound organelles. Both the membrane composition and the [...] Read more.

Cells need to organise and regulate their biochemical processes both in space and time in order to adapt to their surrounding environment. Spatial organisation of cellular components is facilitated by a complex network of membrane bound organelles. Both the membrane composition and the intra-organellar content of these organelles can be specifically and temporally controlled by imposing gates, much like bouncers controlling entry into night-clubs. In addition, a new level of compartmentalisation has recently emerged as a fundamental principle of cellular organisation, the formation of membrane-less organelles. Many of these structures are dynamic, rapidly condensing or dissolving and are therefore ideally suited to be involved in emergency cellular adaptation to stresses. Remarkably, the same proteins have also the propensity to adopt self-perpetuating assemblies which properties fit the needs to encode cellular memory. Here, we review some of the principles of phase separation and the function of membrane-less organelles focusing particularly on their roles during stress response and cellular memory. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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Other

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15 pages, 748 KiB

Open AccessPerspective

Compete or Coexist? Why the Same Mechanisms of Symmetry Breaking Can Yield Distinct Outcomes

by Andrew B. Goryachev and Marcin Leda

Cells 2020, 9(9), 2011; https://doi.org/10.3390/cells9092011 - 1 Sep 2020

Cited by 11 | Viewed by 2548

Abstract

Cellular morphogenesis is governed by the prepattern based on the symmetry-breaking emergence of dense protein clusters. Thus, a cluster of active GTPase Cdc42 marks the site of nascent bud in the baker’s yeast. An important biological question is which mechanisms control the number [...] Read more.

Cellular morphogenesis is governed by the prepattern based on the symmetry-breaking emergence of dense protein clusters. Thus, a cluster of active GTPase Cdc42 marks the site of nascent bud in the baker’s yeast. An important biological question is which mechanisms control the number of pattern maxima (spots) and, thus, the number of nascent cellular structures. Distinct flavors of theoretical models seem to suggest different predictions. While the classical Turing scenario leads to an array of stably coexisting multiple structures, mass-conserved models predict formation of a single spot that emerges via the greedy competition between the pattern maxima for the common molecular resources. Both the outcome and the kinetics of this competition are of significant biological importance but remained poorly explored. Recent theoretical analyses largely addressed these questions, but their results have not yet been fully appreciated by the broad biological community. Keeping mathematical apparatus and jargon to the minimum, we review the main conclusions of these analyses with their biological implications in mind. Focusing on the specific example of pattern formation by small GTPases, we speculate on the features of the patterning mechanisms that bypass competition and favor formation of multiple coexisting structures and contrast them with those of the mechanisms that harness competition to form unique cellular structures. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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10 pages, 1242 KiB

Open AccessEssay

Symmetry Breaking during Cell Movement in the Context of Excitability, Kinetic Fine-Tuning and Memory of Pseudopod Formation

by Peter J.M. van Haastert

Cells 2020, 9(8), 1809; https://doi.org/10.3390/cells9081809 - 30 Jul 2020

Cited by 4 | Viewed by 2514

Abstract

The path of moving eukaryotic cells depends on the kinetics and direction of extending pseudopods. Amoeboid cells constantly change their shape with pseudopods extending in different directions. Detailed analysis has revealed that time, place and direction of pseudopod extension are not random, but [...] Read more.

The path of moving eukaryotic cells depends on the kinetics and direction of extending pseudopods. Amoeboid cells constantly change their shape with pseudopods extending in different directions. Detailed analysis has revealed that time, place and direction of pseudopod extension are not random, but highly ordered with strong prevalence for only one extending pseudopod, with defined life-times, and with reoccurring events in time and space indicative of memory. Important components are Ras activation and the formation of branched F-actin in the extending pseudopod and inhibition of pseudopod formation in the contractile cortex of parallel F-actin/myosin. In biology, order very often comes with symmetry. In this essay, I discuss cell movement and the dynamics of pseudopod extension from the perspective of symmetry and symmetry changes of Ras activation and the formation of branched F-actin in the extending pseudopod. Combining symmetry of Ras activation with kinetics and memory of pseudopod extension results in a refined model of amoeboid movement that appears to be largely conserved in the fast moving Dictyostelium and neutrophils, the slow moving mesenchymal stem cells and the fungus B.d. chytrid. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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19 pages, 5348 KiB

Open AccessPerspective

Size-Regulated Symmetry Breaking in Reaction-Diffusion Models of Developmental Transitions

by Jake Cornwall Scoones, Deb Sankar Banerjee and Shiladitya Banerjee

Cells 2020, 9(7), 1646; https://doi.org/10.3390/cells9071646 - 9 Jul 2020

Cited by 5 | Viewed by 4550

Abstract

The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of self-organisation. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern [...] Read more.

The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of self-organisation. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern and polarity by virtue of local interactions without an upstream supply of information. The combined work of theory and experiment has elucidated how these systems break symmetry during developmental transitions. Given that such transitions are multiple and their temporal ordering is crucial, an equally important question is how these developmental transitions are coordinated in time. Using a minimal mass-conserved substrate-depletion model for symmetry breaking as our case study, we elucidate mechanisms by which cells and tissues can couple reaction–diffusion-driven symmetry breaking to the timing of developmental transitions, arguing that the dependence of patterning mode on system size may be a generic principle by which developing organisms measure time. By analysing different regimes of our model, simulated on growing domains, we elaborate three distinct behaviours, allowing for clock-, timer- or switch-like dynamics. Relating these behaviours to experimentally documented case studies of developmental timing, we provide a minimal conceptual framework to interrogate how developing organisms coordinate developmental transitions. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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18 pages, 1706 KiB

Open AccessPerspective

Why a Large-Scale Mode Can Be Essential for Understanding Intracellular Actin Waves

by Carsten Beta, Nir S. Gov and Arik Yochelis

Cells 2020, 9(6), 1533; https://doi.org/10.3390/cells9061533 - 23 Jun 2020

Cited by 8 | Viewed by 3276

Abstract

During the last decade, intracellular actin waves have attracted much attention due to their essential role in various cellular functions, ranging from motility to cytokinesis. Experimental methods have advanced significantly and can capture the dynamics of actin waves over a large range of [...] Read more.

During the last decade, intracellular actin waves have attracted much attention due to their essential role in various cellular functions, ranging from motility to cytokinesis. Experimental methods have advanced significantly and can capture the dynamics of actin waves over a large range of spatio-temporal scales. However, the corresponding coarse-grained theory mostly avoids the full complexity of this multi-scale phenomenon. In this perspective, we focus on a minimal continuum model of activator–inhibitor type and highlight the qualitative role of mass conservation, which is typically overlooked. Specifically, our interest is to connect between the mathematical mechanisms of pattern formation in the presence of a large-scale mode, due to mass conservation, and distinct behaviors of actin waves. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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9 pages, 1407 KiB

Open AccessOpinion

How Diffusion Impacts Cortical Protein Distribution in Yeasts

by Kyle D. Moran and Daniel J. Lew

Cells 2020, 9(5), 1113; https://doi.org/10.3390/cells9051113 - 30 Apr 2020

Cited by 4 | Viewed by 2978

Abstract

Proteins associated with the yeast plasma membrane often accumulate asymmetrically within the plane of the membrane. Asymmetric accumulation is thought to underlie diverse processes, including polarized growth, stress sensing, and aging. Here, we review our evolving understanding of how cells achieve asymmetric distributions [...] Read more.

Proteins associated with the yeast plasma membrane often accumulate asymmetrically within the plane of the membrane. Asymmetric accumulation is thought to underlie diverse processes, including polarized growth, stress sensing, and aging. Here, we review our evolving understanding of how cells achieve asymmetric distributions of membrane proteins despite the anticipated dissipative effects of diffusion, and highlight recent findings suggesting that differential diffusion is exploited to create, rather than dissipate, asymmetry. We also highlight open questions about diffusion in yeast plasma membranes that remain unsolved. Full article

(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)

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