scholarly journals A mechanochemical model recapitulates distinct vertebrate gastrulation modes

2021 ◽  
Author(s):  
Mattia Serra ◽  
Guillermo Serrano Najera ◽  
Manli Chuai ◽  
Vamsi Spandan ◽  
Cornelis J Weijer ◽  
...  
Keyword(s):  
Phase Space ◽  
Initial Conditions ◽  
Theoretical Framework ◽  
Self Organization ◽  
Critical Event ◽  
Wild Type ◽  
Cellular Processes ◽  
Uniform State ◽  
Mechanochemical Model ◽  
Predictive Theory

Gastrulation is a critical event in vertebrate morphogenesis driven by cellular processes, and characterized by coordinated multi-cellular movements that form the robust morphological structures. How these structures emerge in a developing organism and vary across vertebrates remains unclear. Inspired by experiments on the chick, we derive a theoretical framework that couples actomyosin activity to tissue flow, and provides a basis for the dynamics of gastrulation morphologies. Our model predicts the onset and development of observed experimental patterns of wild-type and perturbations of chick gastrulation as a spontaneous instability of a uniform state. Varying the initial conditions and a parameter in our model, allows us to recapitulate the phase space of gastrulation morphologies seen across vertebrates, consistent with experimental observations in the accompanying paper. All together, this suggests that early embryonic self-organization follows from a minimal predictive theory of active mechano-sensitive flows.

scholarly journals A Framework for Collective Behavior in Plant Inspired Growth-Driven Systems, Based on Kinematics of Allotropism

2019 ◽  
Author(s):  
Renaud Bastien ◽  
Amir Porat ◽  
Yasmine Meroz
Keyword(s):  
Phase Space ◽  
Collective Behavior ◽  
Initial Conditions ◽  
Plant Root ◽  
Growth Dynamics ◽  
Theoretical Framework ◽  
Form Complex ◽  
Main Driver ◽  
Adaptive Structure ◽  
Nearby Point

A variety of biological systems are not motile, but sessile in nature, relying on growth as the main driver of their movement. Groups of such growing organisms can form complex structures, such as the functional architecture of growing axons, or the adaptive structure of plant root systems. These processes are not yet understood, however the decentralized growth dynamics bear similarities to the collective behavior observed in groups of motile organisms, such as flocks of birds or schools of fish. Equivalent growth mechanisms make these systems amenable to a theoretical framework inspired by tropic responses of plants, where growth is considered implicitly as the driver of the observed bending towards a stimulus. We introduce two new concepts related to plant tropisms: point tropism, the response of a plant to a nearby point signal source, and allotropism, the growth-driven response of plant organs to neighboring plants. We first analytically and numerically investigate the 2D dynamics of single organs responding to point signals fixed in space. Building on this we study pairs of organs interacting via allotropism, i.e.each organ senses signals emitted at the tip of their neighbor and responds accordingly. In the case of local sensing we find a rich phase space. We describe the different phases, as well as the sharp transitions between them. We also find that the form of the phase space depends on initial conditions. This work sets the stage towards a theoretical framework for the investigation and understanding of systems of interacting growth-driven individuals.

scholarly journals Self-organized cytoskeletal alignment during Drosophila mesoderm invagination

2020 ◽  
Vol 375 (1809) ◽  
pp. 20190551 ◽  
Author(s):  
Adam C. Martin
Keyword(s):  
Self Organization ◽  
Mechanical Forces ◽  
Feedback Process ◽  
Wild Type ◽  
Tissue Morphogenesis ◽  
Cell Behaviour ◽  
Feedback Mechanisms ◽  
Self Organized ◽  
Actomyosin Cytoskeleton ◽  
Shape Changes

During tissue morphogenesis, mechanical forces are propagated across tissues, resulting in tissue shape changes. These forces in turn can influence cell behaviour, leading to a feedback process that can be described as self-organizing. Here, I discuss cytoskeletal self-organization and point to evidence that suggests its role in directing force during morphogenesis. During Drosophila mesoderm invagination, the shape of the region of cells that initiates constriction creates a mechanical pattern that in turn aligns the cytoskeleton with the axis of greatest resistance to contraction. The wild-type direction of the force controls the shape and orientation of the invaginating mesoderm. Given the ability of the actomyosin cytoskeleton to self-organize, these types of feedback mechanisms are likely to play important roles in a range of different morphogenetic events. This article is part of the discussion meeting issue ‘Contemporary morphogenesis'.

scholarly journals Characterization of Plasmodium falciparum NEDD8 and identification of cullins as its substrates

2020 ◽  
Author(s):  
Manish Bhattacharjee ◽  
Navin Adhikari ◽  
Renu Sudhakar ◽  
Zeba Rizvi ◽  
Divya Das ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Plasmodium Falciparum ◽  
Western Blot ◽  
Wild Type ◽  
Malaria Parasites ◽  
Post Translational Modifications ◽  
Functional Conservation ◽  
Cellular Processes ◽  
Physiological Substrates

ABSTRACTA variety of post-translational modifications of Plasmodium falciparum proteins, including phosphorylation and ubiquitination, are shown to have key regulatory roles. The neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is a ubiquitin-like modifier of cullin-RING E3 ubiquitin ligases, which regulate diverse cellular processes, including the cell-cycle. Although neddylation pathway is conserved in eukaryotes, it is yet to be characterized in Plasmodium and related apicomplexan parasites. Towards studying the neddylation pathway in malaria parasites, we characterized P. falciparum NEDD8 (PfNEDD8) and identified cullins as its physiological substrates. PfNEDD8 is a 76 amino acid residue protein without the C-terminal tail, indicating that it can be readily conjugated. The wild type and mutant (Gly75Gly76 mutated to Ala75Ala76) PfNEDD8 were expressed in P. falciparum. Western blot of wild type PfNEDD8-expressing parasites indicated multiple high molecular weight conjugates, which were absent in the parasites expressing the mutant, indicating conjugation of NEDD8 to proteins through Gly76. Immunoprecipitation followed by mass spectrometry of wild type PfNEDD8-expressing parasites identified several proteins, including two putative cullins. Furthermore, we expressed PfNEDD8 in mutant S. cerevisiae strains that lacked endogenous NEDD8 (Δrub1) or NEDD8 conjugating E2 enzyme (ΔUbc12). The western blot of complemented strains and mass spectrometry of PfNEDD8 immunoprecipitate showed conjugation of PfNEDD8 to S. cerevisiae cullin cdc53, demonstrating functional conservation and cullins as the physiological substrates of PfNEDD8. The characterization of PfNEDD8 and identification of cullins as its substrates make ground for investigation of specific roles and drug target potential of neddylation pathway in malaria parasites.

FGF signalling is required for differentiation-induced cytoskeletal reorganisation and formation of actin-based processes by podocytes

2001 ◽  
Vol 114 (18) ◽  
pp. 3359-3366 ◽  
Author(s):  
Gary Davidson ◽  
Rosanna Dono ◽  
Rolf Zeller
Keyword(s):  
Cell Differentiation ◽  
Actin Cytoskeleton ◽  
Mutant Mouse ◽  
Wild Type Mouse ◽  
Wild Type ◽  
General Role ◽  
Cellular Processes ◽  
Cells In Culture ◽  
Fgf Signalling

To examine the potential role of fibroblast growth factor (FGF) signalling during cell differentiation, we used conditionally immortalised podocyte cells isolated from kidneys of Fgf2 mutant and wild-type mice. Wild-type mouse podocyte cells upregulate FGF2 expression when differentiating in culture, as do maturing podocytes in vivo. Differentiating wild-type mouse podocyte cells undergo an epithelial to mesenchymal-like transition, reorganise their actin cytoskeleton and extend actin-based cellular processes; all of these activities are similar to the activity of podocytes in vivo. Molecular analysis of Fgf2 mutant mouse podocyte cells reveals a general disruption of FGF signalling as expression of Fgf7 and Fgf10 are also downregulated. These FGF mutant mouse podocyte cells in culture fail to activate mesenchymal markers and their post-mitotic differentiation is blocked. Furthermore, mutant mouse podocyte cells in culture fail to reorganise their actin cytoskeleton and form actin-based cellular processes. These studies show that FGF signalling is required by cultured podocytes to undergo the epithelial to mesenchymal-like changes necessary for terminal differentiation. Together with other studies, these results point to a general role for FGF signalling in regulating cell differentiation and formation of actin-based cellular processes during morphogenesis.

Managing to Facilitate Cross-Sectoral Inter-Organizational Collaborations

2020 ◽  
Vol 10 (2) ◽  
pp. 13-41
Author(s):  
Yuki Kawabata
Keyword(s):  
Medical Technology ◽  
Initial Conditions ◽  
The Self ◽  
Management Theory ◽  
Self Organization ◽  
Comprehensive Management ◽  
Technology Industry ◽  
German States ◽  
Organization Process

The promotion of new and competitive industries through cross-sectoral inter-organizational collaborations are tackled in many regions globally. This study explores the management of facilitating collaboration with consideration of the planned approach to change based on change management theory. The “initial conditions,” “field,” and “emerging interaction toward the collaborations” are clarified as key elements for management through intervention. It is considered how these interventions are implemented on these elements. A conceptual model for considering comprehensive management of the self-organization process toward collaboration is proposed. In the case study, experiences of the medical technology industry of three German states are examined. The activities of cluster organizations of these states, which provide services to facilitate cross-sectoral collaborations, are scrutinized. The results of the case study are comparatively analyzed, and the modified conceptual framework is depicted by reflecting the findings of the study. The implications are then discussed.

scholarly journals On the apparent power law in CDM halo pseudo-phase space density profiles

2017 ◽  
Vol 470 (1) ◽  
pp. 500-511 ◽  
Author(s):  
Ethan O. Nadler ◽  
S. Peng Oh ◽  
Suoqing Ji
Keyword(s):  
Phase Space ◽  
Power Law ◽  
Cold Dark Matter ◽  
Initial Conditions ◽  
Phase Space Density ◽  
Fluid Approximation ◽  
Density Profiles ◽  
Space Density ◽  
Scale Free ◽  
Hydrodynamic Calculations

Abstract We investigate the apparent power-law scaling of the pseudo-phase space density (PPSD) in cold dark matter (CDM) haloes. We study fluid collapse, using the close analogy between the gas entropy and the PPSD in the fluid approximation. Our hydrodynamic calculations allow for a precise evaluation of logarithmic derivatives. For scale-free initial conditions, entropy is a power law in Lagrangian (mass) coordinates, but not in Eulerian (radial) coordinates. The deviation from a radial power law arises from incomplete hydrostatic equilibrium (HSE), linked to bulk inflow and mass accretion, and the convergence to the asymptotic central power-law slope is very slow. For more realistic collapse, entropy is not a power law with either radius or mass due to deviations from HSE and scale-dependent initial conditions. Instead, it is a slowly rolling power law that appears approximately linear on a log–log plot. Our fluid calculations recover PPSD power-law slopes and residual amplitudes similar to N-body simulations, indicating that deviations from a power law are not numerical artefacts. In addition, we find that realistic collapse is not self-similar; scalelengths such as the shock radius and the turnaround radius are not power-law functions of time. We therefore argue that the apparent power-law PPSD cannot be used to make detailed dynamical inferences or extrapolate halo profiles inwards, and that it does not indicate any hidden integrals of motion. We also suggest that the apparent agreement between the PPSD and the asymptotic Bertschinger slope is purely coincidental.

scholarly journals Data-Driven Models Reveal Mutant Cell Behaviors Important for Myxobacterial Aggregation

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Zhaoyang Zhang ◽  
Christopher R. Cotter ◽  
Zhe Lyu ◽  
Lawrence J. Shimkets ◽  
Oleg A. Igoshin
Keyword(s):  
Cell Tracking ◽  
Mutant Cell ◽  
Myxococcus Xanthus ◽  
Data Driven ◽  
Self Organization ◽  
Cell Behavior ◽  
Significant Heterogeneity ◽  
Wild Type ◽  
Content Type ◽  
Mutant Strains

ABSTRACT Single mutations frequently alter several aspects of cell behavior but rarely reveal whether a particular statistically significant change is biologically significant. To determine which behavioral changes are most important for multicellular self-organization, we devised a new methodology using Myxococcus xanthus as a model system. During development, myxobacteria coordinate their movement to aggregate into spore-filled fruiting bodies. We investigate how aggregation is restored in two mutants, csgA and pilC, that cannot aggregate unless mixed with wild-type (WT) cells. To this end, we use cell tracking to follow the movement of fluorescently labeled cells in combination with data-driven agent-based modeling. The results indicate that just like WT cells, both mutants bias their movement toward aggregates and reduce motility inside aggregates. However, several aspects of mutant behavior remain uncorrected by WT, demonstrating that perfect recreation of WT behavior is unnecessary. In fact, synergies between errant behaviors can make aggregation robust. IMPORTANCE Self-organization into spatial patterns is evident in many multicellular phenomena. Even for the best-studied systems, our ability to dissect the mechanisms driving coordinated cell movement is limited. While genetic approaches can identify mutations perturbing multicellular patterns, the diverse nature of the signaling cues coupled to significant heterogeneity of individual cell behavior impedes our ability to mechanistically connect genes with phenotype. Small differences in the behaviors of mutant strains could be irrelevant or could sometimes lead to large differences in the emergent patterns. Here, we investigate rescue of multicellular aggregation in two mutant strains of Myxococcus xanthus mixed with wild-type cells. The results demonstrate how careful quantification of cell behavior coupled to data-driven modeling can identify specific motility features responsible for cell aggregation and thereby reveal important synergies and compensatory mechanisms. Notably, mutant cells do not need to precisely recreate wild-type behaviors to achieve complete aggregation.

scholarly journals Relevance of STK11 Mutations Regarding Immune Cell Infiltration, Drug Sensitivity, and Cellular Processes in Lung Adenocarcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhenqing Li ◽  
Bo Ding ◽  
Jianxun Xu ◽  
Kai Mao ◽  
Pengfei Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Drug Sensitivity ◽  
Immune Cell ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Wild Type ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cellular Processes

Serine/threonine kinase 11 (STK11) is one member of the serine/threonine kinase family, which is involved in regulating cell polarity, apoptosis, and DNA damage repair. In lung adenocarcinoma (LUAD), it can play as one tumor suppressor and always be mutated. In this study, we aimed to assess the relevance of STK11 mutations in LUAD, in which we also studied the correlation among immune cell infiltration, drug sensitivity, and cellular processes. By performing the bioinformatics analysis of the Cancer Genome Atlas (TCGA) about LUAD patients, we found that the mutation efficiency of STK11 mutations is about 19%. Additionally, the differentially expressed gene analysis showed that there were 746 differentially expressed genes (DEGs) between LUAD patients with and without STK11 mutations. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis showed that the DEGs were enriched in various tumorigenesis signaling pathways and metabolic processes. Among these DEGs, the top ranking 21 genes were found that they were more frequently mutated in the STK11 mutation group than in the wild-type group (p-value<0.01). Finally, the LUAD patients with STK11 mutations suffered the worse immune cell infiltration levels than the LUAD patients with wild-type. The STK11 gene copy number was correlated with immune cell infiltration. Aiming to develop the therapeutic drugs, we performed Genomics of Drug Sensitivity in Cancer (GDSC) data to identify the potential therapeutic candidate and the results showed that Nutlin-3a(-) may be a sensitive drug for LUAD cases harboring STK11 mutations. The specific genes and pathways shown to be associated with LUAD cases involving STK11 mutations may serve as targets for individualized LUAD treatment.

scholarly journals Huntington’s Disease—An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1514 ◽  
Author(s):  
Aleksandra S. Taran ◽  
Lilia D. Shuvalova ◽  
Maria A. Lagarkova ◽  
Irina B. Alieva
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Autosomal Dominant ◽  
Cell Physiology ◽  
Mutant Form ◽  
Striatal Neurons ◽  
Molecular Processes ◽  
Wild Type ◽  
Cellular Processes ◽  
Cell Structures

Huntington’s disease is a severe and currently incurable neurodegenerative disease. An autosomal dominant mutation in the Huntingtin gene (HTT) causes an increase in the polyglutamine fragment length at the protein N-terminus. The consequence of the mutation is the death of neurons, mostly striatal neurons, leading to the occurrence of a complex of motor, cognitive and emotional-volitional personality sphere disorders in carriers. Despite intensive studies, the functions of both mutant and wild-type huntingtin remain poorly understood. Surprisingly, there is the selective effect of the mutant form of HTT even on nervous tissue, whereas the protein is expressed ubiquitously. Huntingtin plays a role in cell physiology and affects cell transport, endocytosis, protein degradation and other cellular and molecular processes. Our experimental data mining let us conclude that a significant part of the Huntingtin-involved cellular processes is mediated by microtubules and other cytoskeletal cell structures. The review attempts to look at unresolved issues in the study of the huntingtin and its mutant form, including their functions affecting microtubules and other components of the cell cytoskeleton.

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