From heterogeneous morphogenetic fields to homogeneous regions as a step towards understanding complex tissue dynamics

Development ◽  
2021 ◽  
Vol 148 (23) ◽  
Author(s):  
Satoshi Yamashita ◽  
Boris Guirao ◽  
François Graner

ABSTRACT Within developing tissues, cell proliferation, cell motility and other cell behaviors vary spatially, and this variability gives a complexity to the morphogenesis. Recently, novel formalisms have been developed to quantify tissue deformation and underlying cellular processes. A major challenge for the study of morphogenesis now is to objectively define tissue sub-regions exhibiting different dynamics. Here, we propose a method to automatically divide a tissue into regions where the local deformation rate is homogeneous. This was achieved by several steps including image segmentation, clustering and region boundary smoothing. We illustrate the use of the pipeline using a large dataset obtained during the metamorphosis of the Drosophila pupal notum. We also adapt it to determine regions in which the time evolution of the local deformation rate is homogeneous. Finally, we generalize its use to find homogeneous regions for cellular processes such as cell division, cell rearrangement, or cell size and shape changes. We also illustrate it on wing blade morphogenesis. This pipeline will contribute substantially to the analysis of complex tissue shaping, and the biochemical and biomechanical regulations driving tissue morphogenesis.

2019 ◽  
Author(s):  
Satoshi Yamashita ◽  
Boris Guirao ◽  
François Graner

AbstractWithin developing tissues, cell proliferation, cell motility, and other cell behaviors vary spatially, and this variability gives a complexity to the morphogenesis. Recently, novel formalisms have been developed to quantify tissue deformation and underlying cellular processes. A major challenge for the study of morphogenesis now is to objectively define tissue sub-regions exhibiting different dynamics. Here we propose a method to automatically divide a tissue into regions where the local deformation rate is homogeneous. This was achieved by several steps including image segmentation, clustering, and region boundary smoothing. We illustrate the use of the pipeline using a large dataset obtained during the metamorphosis of the Drosophila pupal notum. We also adapt it to determine regions where the time evolution of the local deformation rate is homogeneous. Finally, we generalize its use to find homogeneous regions for the cellular processes such as cell division, cell rearrangement, or cell size and shape changes. We also illustrate it on wing blade morphogenesis. This pipeline will contribute substantially to the analysis of complex tissue shaping and the biochemical and bio-mechanical regulations driving tissue morphogenesis.


2018 ◽  
Vol 19 (10) ◽  
pp. 2872 ◽  
Author(s):  
Monika Janczarek ◽  
José-María Vinardell ◽  
Paulina Lipa ◽  
Magdalena Karaś

Reversible phosphorylation is a key mechanism that regulates many cellular processes in prokaryotes and eukaryotes. In prokaryotes, signal transduction includes two-component signaling systems, which involve a membrane sensor histidine kinase and a cognate DNA-binding response regulator. Several recent studies indicate that alternative regulatory pathways controlled by Hanks-type serine/threonine kinases (STKs) and serine/threonine phosphatases (STPs) also play an essential role in regulation of many different processes in bacteria, such as growth and cell division, cell wall biosynthesis, sporulation, biofilm formation, stress response, metabolic and developmental processes, as well as interactions (either pathogenic or symbiotic) with higher host organisms. Since these enzymes are not DNA-binding proteins, they exert the regulatory role via post-translational modifications of their protein targets. In this review, we summarize the current knowledge of STKs and STPs, and discuss how these enzymes mediate gene expression in prokaryotes. Many studies indicate that regulatory systems based on Hanks-type STKs and STPs play an essential role in the regulation of various cellular processes, by reversibly phosphorylating many protein targets, among them several regulatory proteins of other signaling cascades. These data show high complexity of bacterial regulatory network, in which the crosstalk between STK/STP signaling enzymes, components of TCSs, and the translational machinery occurs. In this regulation, the STK/STP systems have been proved to play important roles.


2012 ◽  
Vol 199 (1) ◽  
pp. 169-185 ◽  
Author(s):  
Rui Duan ◽  
Peng Jin ◽  
Fengbao Luo ◽  
Guofeng Zhang ◽  
Nathan Anderson ◽  
...  

The p21-activated kinases (PAKs) play essential roles in diverse cellular processes and are required for cell proliferation, apoptosis, polarity establishment, migration, and cell shape changes. Here, we have identified a novel function for the group I PAKs in cell–cell fusion. We show that the two Drosophila group I PAKs, DPak3 and DPak1, have partially redundant functions in myoblast fusion in vivo, with DPak3 playing a major role. DPak3 is enriched at the site of fusion colocalizing with the F-actin focus within a podosome-like structure (PLS), and promotes actin filament assembly during PLS invasion. Although the small GTPase Rac is involved in DPak3 activation and recruitment to the PLS, the kinase activity of DPak3 is required for effective PLS invasion. We propose a model whereby group I PAKs act downstream of Rac to organize the actin filaments within the PLS into a dense focus, which in turn promotes PLS invasion and fusion pore initiation during myoblast fusion.


2020 ◽  
Vol 21 (3) ◽  
pp. 1106 ◽  
Author(s):  
Sruthi V. Hindupur ◽  
Sebastian C. Schmid ◽  
Jana Annika Koch ◽  
Ahmed Youssef ◽  
Eva-Maria Baur ◽  
...  

The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.


2008 ◽  
Vol 190 (7) ◽  
pp. 2588-2596 ◽  
Author(s):  
Mario J. Borgnia ◽  
Sriram Subramaniam ◽  
Jacqueline L. S. Milne

ABSTRACT Bdellovibrio bacteriovorus cells are small deltaproteobacterial cells that feed on other gram-negative bacteria, including human pathogens. Using cryo-electron tomography, we demonstrated that B. bacteriovorus cells are capable of substantial flexibility and local deformation of the outer and inner membranes without loss of cell integrity. These shape changes can occur in less than 2 min, and analysis of the internal architecture of highly bent cells showed that the overall distribution of molecular machines and the nucleoid is similar to that in moderately bent cells. B. bacteriovorus cells appear to contain an extensive internal network of short and long filamentous structures. We propose that rearrangements of these structures, in combination with the unique properties of the cell envelope, may underlie the remarkable ability of B. bacteriovorus cells to find and enter bacterial prey.


e-Polymers ◽  
2014 ◽  
Vol 14 (5) ◽  
pp. 297-304
Author(s):  
Guo-xun Chang ◽  
Ke-feng Ren ◽  
Yi-xiu Zhao ◽  
Yi-xin Sun ◽  
Jian Ji

AbstractIn addition to the topographical features and chemical properties of substrates, the mechanical properties are known as a vital regulator of cellular processes such as adhesion, proliferation, and migration, and have received considerable attention in recent years. In this work, electrochemical redox multilayers made of ferrocene-modified poly(ethylenimine) (PEI-Fc) and deoxyribonucleic acid (DNA) with controlled stiffness were used to investigate the effects of the mechanical properties of multilayers on fibroblast cell (NIH/3T3) behaviors. Redox PEI-Fc plays an essential role in inducing swelling in multilayers under an electrochemical stimulus, resulting in distinct changes in the stiffness of the multilayers. The Young’s modulus varied from 2.05 to 1.07 MPa for the (PEI-Fc/DNA) multilayers by changing the oxidation time of the electrochemical treatment. We demonstrated that the adhesion, proliferation, and migration of fibroblast cells depended on the multilayers’ stiffness. These results indicate that cell behaviors can be precisely controlled by electrochemical treatment, which provides a new way to prepare thin films with tunable mechanical properties with potential biomedical applications.


2018 ◽  
Author(s):  
Juliana Antonipillai ◽  
Sheena Rigby ◽  
Nicole Bassler ◽  
Karlheinz Peter ◽  
Ora Bernard

AbstractActin is highly abundant in platelets, and platelet function is dependent on actin structures. Actin filaments are dynamic structures involved in many cellular processes including platelet shape changes and adhesion. The actin cytoskeleton is tightly regulated by actin-binding proteins, which include the members of the actin depolymerising factor (ADF)/cofilin family. LIM kinase (LIMK) and slingshot phosphatase (SSH-1L) regulate actin dynamics by controlling the binding affinity of ADF/cofilin towards actin. We hypothesised that inhibition of LIMK activity may prevent the changes in platelet shape during their activation and therefore their function by controlling the dynamics of Factin. Therefore, inhibition of LIMK activity may represent an attractive new strategy to control and inhibit platelet function; particularly the formation of stable platelet aggregates and thus stable thrombi.


1992 ◽  
Vol 263 (1) ◽  
pp. H293-H306 ◽  
Author(s):  
E. K. Rodriguez ◽  
W. C. Hunter ◽  
M. J. Royce ◽  
M. K. Leppo ◽  
A. S. Douglas ◽  
...  

The ability to measure cyclic changes in myocardial sarcomere lengths and orientations during cardiac ejection and filling would improve our understanding of how the cellular processes of contraction relate to the pumping of the whole heart. Previously, only postmortem sarcomere measurements were possible after arresting the heart in one state and fixing it for histology. By combining such histological measurements with direct observations of the deformation experienced by the same myocardial region while the heart was beating, we have developed a method to reconstruct sarcomere lengths and orientations throughout the cardiac cycle and at several transmural layers. A set of small (1 mm) radiopaque beads was implanted in approximately 1 cm3 of the left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles. To quantify local myocardial deformation (as revealed by the relative motion of the markers), we calculated the local deformation gradient tensors. As the heart deforms, these describe how any short vectorial line segment alters its length and orientation relative to a reference state. Specifically, by choosing the reference state to be the arrested and fixed heart and by measuring the sarcomere vector in that state, we could then use the deformation gradient tensors to reconstruct the sarcomere vector that would exist in the beating heart. As ventricular chamber volume varied over its normal range of operation, the range of reconstructed sarcomere lengths (approximately 1.7-2.4 microns) was comparable to other histological studies and to measurements of sarcomere length in excised papillary muscles or trabeculae. The pattern of sarcomere length changes was markedly different, however, during ejection vs. filling.


2005 ◽  
Vol 169 (5) ◽  
pp. 777-787 ◽  
Author(s):  
Fang Lin ◽  
Diane S. Sepich ◽  
Songhai Chen ◽  
Jacek Topczewski ◽  
Chunyue Yin ◽  
...  

Gα12/13 have been implicated in numerous cellular processes, however, their roles in vertebrate gastrulation are largely unknown. Here, we show that during zebrafish gastrulation, suppression of both Gα12 and Gα13 signaling by overexpressing dominant negative proteins and application of antisense morpholino-modified oligonucleotide translation interference disrupted convergence and extension without changing embryonic patterning. Analyses of mesodermal cell behaviors revealed that Gα12/13 are required for cell elongation and efficient dorsalward migration during convergence independent of noncanonical Wnt signaling. Furthermore, Gα12/13 function cell-autonomously to mediate mediolateral cell elongation underlying intercalation during notochord extension, likely acting in parallel to noncanonical Wnt signaling. These findings provide the first evidence that Gα12 and Gα13 have overlapping and essential roles in distinct cell behaviors that drive vertebrate gastrulation.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262632
Author(s):  
Tsukasa Nakatoh ◽  
Takuji Osaki ◽  
Sohma Tanimoto ◽  
Md. Golam Sarowar Jahan ◽  
Tomohisa Kawakami ◽  
...  

In the field of cell and tissue engineering, there is an increasing demand for techniques to spatially control the adhesion of cells to substrates of desired sizes and shapes. Here, we describe two novel methods for fabricating a substrate for adhesion of cells to a defined area. In the first method, the surface of the coverslip or plastic dish was coated with Lipidure, a non-adhesive coating material, and air plasma was applied through a mask with holes, to confer adhesiveness to the surface. In the second method, after the surface of the coverslip was coated with gold by sputtering and then with Lipidure; the Lipidure coat was locally removed using a novel scanning laser ablation method. These methods efficiently confined cells within the adhesive area and enabled us to follow individual cells for a longer duration, compared to the currently available commercial substrates. By following single cells within the confined area, we were able to observe several new aspects of cell behavior in terms of cell division, cell–cell collisions, and cell collision with the boundary between adhesive and non-adhesive areas.


Sign in / Sign up

Export Citation Format

Share Document