Menu

Close

Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, Kristen Marie Kwan, George Thomas Eisenhoffer Jr.

Preprint posted on May 17, 2018 https://www.biorxiv.org/content/early/2018/05/17/324301

How do biophysical cues control cell behaviour during tissue repair? This recent preprint employs high resolution live imaging of regenerating zebrafish tissue to provide new insight into the tension-induced changes underlying successful wound repair

Selected by Helen Weavers

Context

Following injury, tissues rapidly initiate a multi-step repair process to restore tissue architecture. Effective repair requires precise control of the cell number within the tissue – and this means that tissue-wide levels of cell proliferation and elimination must be tightly coordinated. Given that adjacent cells in epithelial tissues are physically linked, any changes to individual cells can have profound long-range mechanical and behavioural effects on surrounding cells. Although mechanical forces are well known to regulate cell behaviours during tissue morphogenesis1, whether these mechanical forces play important roles in regulating cell behaviours across a repairing epithelial sheet is currently less well understood.

Key findings

In this interesting preprint, Franco et al use high resolution time-lapse imaging of zebrafish larvae to analyse the changes in cell behaviour that occur at an individual and tissue-wide level during epithelial repair. These live-imaging studies following surgical amputation of the zebrafish tail (Figure 1, A before and B after amputation) reveal there is a strict spatial regulation of cell elimination and proliferation across the regenerating tissue. Whilst injury causes a dramatic increase in the extrusion of non-apoptotic cells in crowded areas near the wound edge (see Figure 1; GFP labelled actin), cell proliferation occurs preferentially in separate non-crowded areas much further back. But are these distinct cell behaviours linked to changes in tissue mechanics? By both applying specialised CellFIT software2  to infer cellular tension and measuring cell density, the authors could correlate changes in tension (Figure 2) and crowding with these specific cell behaviours.

Figure 1: Taken from Figure 1A of the preprint showing live imaging of (A) non-amputated and (B) amputated 4 day post-fertilization (dpf) zebrafish larvae expressing LifeAct-GFP.

Figure 2: Taken from Figure 1G-H of the preprint showing tension maps generated using CellFIT software from live-imaging of non-amputated (G) and amputated (H) zebrafish larvae.

How then, do epithelial cells detect such changes in crowding and tissue tension? Strikingly, experimental disruption of mechanically-regulated stretch-activated ion channels (SACs) caused dramatic effects on cell behaviour; by disrupting the cells ability to sense mechanical forces, cells failed to extrude from crowded areas of the tissue and these areas even experienced aberrant proliferation. Thus, successful tissue regeneration relies on the ability of epithelial cells to sense mechanical forces though the activity of SACs, in order to spatially and temporally coordinate cell extrusion and proliferation across a repairing epithelial sheet.

Future directions

This work raises many fascinating questions for future research. What signalling pathways lie downstream of the SAC activity in response to crowding or increased tissue tension to elicit these different cellular responses? Could such mechano-signalling pathways be exploited in the clinic to improve the repair of chronic wounds that fail to heal? Given my own interests in field of injury-induced inflammation, I’m also intrigued as to the fate of the extruded epithelial cells – are these eliminated cells cleared by phagocytic cells of the zebrafish innate immune system or do they persist and contribute to tissue repair in other ways? Moreover, if immune cells are involved, does phagocytic clearance of these cells have a critical role in the extrusion and regeneration process itself?

References

  1. Heisenberg, CP. And Bellaiche, Y. 2013. Forces in tissue morphogenesis and patterning. Cell. 153:948-62.
  2. Brodland, GW., Veldhuis, JH., Kim, S., Perrone, M., Mashburn, D. and Hutson, MS. 2014. CellFIT: a cellular force-inference toolkit using curvilinear cell boundaries. PloS One. 9:e99116.

Tags: live-imaging, zebrafish; regeneration; wound repair; tissue mechanics; morphogenesis; cell migration; cell death

Posted on: 4th June 2018

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the biophysics category:

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    Dynamics and interactions of ADP/ATP transporter AAC3 in DPC detergent are not functionally relevant

    Vilius Kurauskas, Audrey Hessel, François Dehez, et al.

    AND

    Major concerns with the integrity of the mitochondrial ADP/ATP carrier in dodecyl-phosphocholine used for solution NMR studies

    Martin S. King, Paul G. Crichton, Jonathan J. Ruprecht, et al.



    Selected by Reid Alderson

    1

    Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

    K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, et al.



    Selected by Ivana Viktorinová

    Kinetic sculpting of the seven stripes of the Drosophila even-skipped gene

    Augusto Berrocal, Nicholas C Lammers, Hernan G Garcia, et al.



    Selected by Erik Clark

    Structural Basis of Tubulin Recruitment and Assembly by Tumor Overexpressed Gene (TOG) domain array Microtubule Polymerases

    Stanley Nithiananatham, Brian Cook, Fred Chang, et al.

    AND

    Roles for tubulin recruitment and self-organization by TOG domain arrays in Microtubule plus-end tracking and polymerase

    Brian Cook, Fred Chang, Ignacio Flor-Parra, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    Clathrin plaques form mechanotransducing platforms

    Agathe Franck, Jeanne Laine, Gilles Moulay, et al.



    Selected by Amanda Haage

    Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

    Daniel R. Kattnig, Claus Nielsen, Ilia A. Solov'yov



    Selected by Miriam Liedvogel

    1

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    Tissue flow induces cell shape changes during organogenesis

    Gonca Erdemci-Tandogan, Madeline J.Clark, Jeffrey D. Amack, et al.



    Selected by Jacky G. Goetz

    Two contractile pools of actomyosin distinctly load and tune E-cadherin levels during morphogenesis

    Girish R. Kale, Xingbo Yang, Jean-Marc Philippe, et al.



    Selected by Arnaud Monnard

    Feedback control of neurogenesis by tissue packing

    Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, et al.



    Selected by Sarah Morson

    1

    Tunable molecular tension sensors reveal extension-based control of vinculin loading

    Andrew S LaCroix, Andrew D Lynch, Matthew E Berginski, et al.



    Selected by Amanda Haage

    1

    Also in the cell biology category:

    The cytoskeleton as a smart composite material: A unified pathway linking microtubules, myosin-II filaments and integrin adhesions

    Nisha Mohd Rafiq, Yukako Nishimura, Sergey V. Plotnikov, et al.



    Selected by Coert Margadant

    Quantitative, real-time, single cell analysis in tissue reveals expression dynamics of neurogenesis

    Cerys S Manning, Veronica Biga, James Boyd, et al.



    Selected by Teresa Rayon

    Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

    Junnian Wei, Kevin K. Leung, Charles Truillet, et al.



    Selected by Rob Hynds

    1

    Optogenetic dissection of mitotic spindle positioning in vivo

    Lars-Eric Fielmich, Ruben Schmidt, Daniel J Dickinson, et al.



    Selected by Angika Basant

    1

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    A limited number of double-strand DNA breaks are sufficient to delay cell cycle progression.

    Jeroen van den Berg, Anna G. Manjon, Karoline Kielbassa, et al.



    Selected by Leighton Daigh

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos

    JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine

    Daniel Hu, Heinrich Jasper



    Selected by Maiko Kitaoka

    ER-to-Golgi trafficking of procollagen in the absence of large carriers.

    Janine McCaughey, Nicola Stevenson, Stephen Cross, et al.



    Selected by Gautam Dey

    1

    Template switching causes artificial junction formation and false identification of circular RNAs

    Chong Tang, Tian Yu, Yeming Xie, et al.



    Selected by Fabio Liberante

    Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

    K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, et al.



    Selected by Ivana Viktorinová

    Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon

    Jessica Messier, Hongmei Chen, Zhao-Lin Cai, et al.

    AND

    High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

    Mathias Mahn, Lihi Gibor, Katayun Cohen-Kashi Malina, et al.



    Selected by Mahesh Karnani

    2

    EFFECTORS OF THE SPINDLE ASSEMBLY CHECKPOINT BUT NOT THE MITOTIC EXIT NETWORK ARE CONFINED WITHIN THE NUCLEUS OF SACCHAROMYCES CEREVISIAE

    Lydia R Heasley, Jennifer G DeLuca, Steven M Markus



    Selected by Hiral Shah

    An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

    Ilias Angelidis, Lukas M Simon, Isis E Fernandez, et al.



    Selected by Rob Hynds

    1

    Peculiar features of the plastids of the colourless alga Euglena longa and photosynthetic euglenophytes unveiled by transcriptome analyses

    Kristina Zahonova, Zoltan Fussy, Erik Bircak, et al.



    Selected by Ellis O'Neill

    1

    Also in the developmental biology category:

    LADL: Light-activated dynamic looping for endogenous gene expression control

    Mayuri Rege, Ji Hun Kim, Jacqueline Valeri, et al.



    Selected by Ivan Candido-Ferreira

    Quantitative, real-time, single cell analysis in tissue reveals expression dynamics of neurogenesis

    Cerys S Manning, Veronica Biga, James Boyd, et al.



    Selected by Teresa Rayon

    The cis-regulatory logic underlying abdominal Hox-mediated repression versus activation of regulatory elements in Drosophila



    Selected by Clarice Hong

    1

    Optogenetic dissection of mitotic spindle positioning in vivo

    Lars-Eric Fielmich, Ruben Schmidt, Daniel J Dickinson, et al.



    Selected by Angika Basant

    1

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    A transition from SoxB1 to SoxE transcription factors is essential for progression from pluripotent blastula cells to neural crest cells

    Elsy Buitrago-Delgado, Elizabeth Schock, Kara Nordin, et al.



    Selected by Amanda Haage

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish

    Themistoklis M. Tsarouchas, Daniel Wehner, Leonardo Cavone, et al.



    Selected by Shikha Nayar

    1

    JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine

    Daniel Hu, Heinrich Jasper



    Selected by Maiko Kitaoka

    ER-to-Golgi trafficking of procollagen in the absence of large carriers.

    Janine McCaughey, Nicola Stevenson, Stephen Cross, et al.



    Selected by Gautam Dey

    1

    Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

    K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, et al.



    Selected by Ivana Viktorinová

    A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion

    Richard W Naylor, Alan J Davidson



    Selected by Giuliana Clemente

    1

    An intrinsic cell cycle timer terminates limb bud outgrowth

    Joseph Pickering, Kavitha Chinnaiya, Constance A Rich, et al.



    Selected by Ashrifia Adomako-Ankomah

    1

    Fbxw7 is a critical regulator of Schwann cell myelinating potential

    Breanne L Harty, Fernanda Coelho, Sarah D Ackerman, et al.



    Selected by Yen-Chung Chen

    Kinetic sculpting of the seven stripes of the Drosophila even-skipped gene

    Augusto Berrocal, Nicholas C Lammers, Hernan G Garcia, et al.



    Selected by Erik Clark

    TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila.

    Byoungchun Lee, Elizabeth C Barretto, Savraj S Grewal



    Selected by Sarah Bowling

    Also in the genetics category:

    The cis-regulatory logic underlying abdominal Hox-mediated repression versus activation of regulatory elements in Drosophila



    Selected by Clarice Hong

    1

    Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish

    Themistoklis M. Tsarouchas, Daniel Wehner, Leonardo Cavone, et al.



    Selected by Shikha Nayar

    1

    JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine

    Daniel Hu, Heinrich Jasper



    Selected by Maiko Kitaoka

    Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions

    Summer B. Thyme, Lindsey M. Pieper, Eric H. Li, et al.



    Selected by Daniel Grimes

    Super-Mendelian inheritance mediated by CRISPR/Cas9 in the female mouse germline

    Hannah A. Grunwald, Valentino M. Gantz, Gunnar Poplawski, et al.



    Selected by Rebekah Tillotson

    1

    The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization

    Sarah Herberg, Krista R Gert, Alexander Schleiffer, et al.



    Selected by James Gagnon

    Functional testing of a human PBX3 variant in zebrafish reveals a potential modifier role in congenital heart defects

    Gist H. Farr III, Kimia Imani, Darren Pouv, et al.



    Selected by Hannah Brunsdon

    A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins

    David Booth, Heather Middleton, Nicole King



    Selected by Maya Emmons-Bell

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    Genetic compensation is triggered by mutant mRNA degradation

    Mohamed El-Brolosy, Andrea Rossi, Zacharias Kontarakis, et al.



    Selected by Andreas van Impel

    1

    Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

    Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, et al.



    Selected by Helen Weavers

    Limb- and tendon-specific Adamtsl2 deletion identifies a soft tissue mechanism modulating bone length

    Dirk Hubmacher, Stetson Thacker, Sheila M Adams, et al.



    Selected by Alberto Rosello-Diez

    Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)

    Scott J Callahan, Stephanie Tepan, Yan M Zhang, et al.



    Selected by Hannah Brunsdon

    1

    PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

    Nathalie Conte, Jeremy Mason, Csaba Halmagyi, et al.



    Selected by Carmen Adriaens

    Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin

    Jacob Daane, Jennifer Lanni, Ina Rothenberg, et al.



    Selected by Alberto Rosello-Diez

    1

    Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of cell division, differentiation, and loss

    Judy Martin, Erin Nicole Sanders, Paola Moreno-Roman, et al.



    Selected by Natalie Dye
    Close