Close
Close

preLights is supported by…

Related posts

Related preLists

Mechanical cues organize planar cell polarity during vertebrate morphogenesis and embryonic wound repair

Chih-Wen Chu, Satheeja Velayudhan, Jakob H. Schauser, Sapna Krishnakumar, Stephanie Yang, Keiji Itoh, Dominique Alfandari, Ala Trusina, Sergei Y. Sokol

Posted on: 2 July 2025

Preprint posted on 21 May 2025

Article now published in Current Biology at https://www.sciencedirect.com/science/article/pii/S0960982225006852?via%3Dihub

Stretch it, wound it, pull it: ADIP-Diversin polarizes anyway. Characterization of a new mechanosensitive polarity module.

Selected by Aline Grata

Categories: cell biology

Background
During embryonic development, large-scale tissue remodeling events such as neural tube closure or germ band extension rely on the coordinated movement of cells in response to mechanical and molecular cues. Cells can generate and respond to forces via cytoskeletal networks and adhesion complexes, but how local mechanical inputs are translated into long-range, coordinated cellular behaviors remains elusive.
Planar cell polarity (PCP) signaling is a candidate mechanism for organizing such collective behaviors, as it aligns cells along the plane of a tissue and has been linked to morphogenetic events. PCP involves feedback-driven polarization of core proteins and interacts with cytoskeletal regulators like F-actin and Myosin II. Moreover, evidence suggests that mechanical forces can influence PCP establishment. Nonetheless, it is still unclear whether PCP signaling senses mechanical forces.
Addressing this gap using the Xenopus embryonic ectoderm, the authors of this preprint focus on a previously identified protein, ADIP, as a potential mechanosensitive component. They identify ADIP as a key player in linking mechanical inputs to PCP signaling, suggesting that it responds to tissue tension in vivo and interacts with the PCP protein Diversin to drive polarized signaling under mechanical stress, both during morphogenetic events and in wound healing.

 

Key findings

1.ADIP localization is polarized in epithelia under stress.
The authors observed that ADIP localization within tissues changes in response to mechanical forces. Under relaxed conditions, ADIP appears in randomly distributed punctae, but in cells near regions of apical constriction (such as around the neural tube or blastopore) it polarizes toward the site of constriction. This suggests that ADIP might be mechanically regulated. To test this, the authors applied controlled mechanical forces through genetic and physical manipulations. In all cases, ADIP polarized along the direction of force, and this response was dependent on Myosin II activity, confirming a force-sensitive, MyoII-dependent mechanism of ADIP polarization.
The authors then switched to wound healing, by removing a piece of the gastrula ectoderm. Within 20-40 minutes, ADIP was re-localized in punctae towards the site of the wound, further confirming the mechanosensitive nature of its localization.

 

 

2. ADIP polarization requires its interaction with α-Actinin
In order to characterize which domain of the protein is required for this mechanosensing ability, the authors generated mutant forms of the protein lacking the Afadin binding domain or the α-actinin binding domain. They proceeded by expressing these mutant forms in the wounded ectoderm, and observed that, while the mutant lacking Afadin-binding site still polarized, the one lacking the α-actinin binding-region failed to polarize towards the wound, leading them to conclude that α-actinin is involved in ADIP polarization.

 

3. ADIP is required for wound healing
To explore the relevance of ADIP polarization upon wounding, they depleted embryos of ADIP and induced wounds. ADIP morphant embryos exhibited a slower rate of wound closure compared to control conditions, and that could be rescued by expressing ADIP RNA. Moreover, ADIP-depleted embryos exhibited reduced F-actin and E-Cadherin, suggesting that ADIP might be involved in adherens junctions assembly or maintenance.

 

4. ADIP forms a complex with Diversin to establish PCP upon wounding
Because the polarization pattern of ADIP is reminiscent of that of PCP proteins, the authors investigated markers that become similarly polarized around the wound and identified the PCP protein Diversin. They observed that ADIP and Diversin form a complex, evidence supported both by their co-localization and by a proximity-labeling assay. Diversin responds to mechanical cues by associating with ADIP, and that Diversin is required for ADIP localization.

 

What I like about the preprint
What I appreciated about this preprint is the creative and varied use of techniques to investigate ADIP’s mechanosensitive polarization across multiple biological contexts, including two distinct morphogenetic processes and wound healing. These diverse experiments robustly support ADIP’s role as a mechanosensor, and suggest that the phenomenon is robust across diverse biological contexts.
Beyond the techniques, I also found the conceptual direction of the paper exciting. The idea that a mechanosensitive protein like ADIP might link physical cues to planar cell polarity (PCP) signaling is highly relevant, especially given PCP’s roles in collective cell behavior during development and disease. While the study does not yet provide a full mechanistic dissection, I think that’s part of what makes it so promising. The work raises several important questions that could shape future research.

Tags: forces, polarity, xenopus

doi: https://doi.org/10.1242/prelights.40982

Read preprint (No Ratings Yet)

Author's response

Chih-Wen Chu, Satheeja Velayudhan and Sergei Y. Sokol shared

  1. Your manipulations in this study involve large-scale mechanical inputs (apical constriction in clusters of cells, whole-embryo stretching, wounding). Do you think smaller-scale mechanical events, like the localized apical constriction that occurs during epithelial cell extrusion, could be sufficient to trigger ADIP-Diversin polarization? I’d be curious to hear your thoughts on how sensitive this response might be to the scale or geometry of force.

Our unpublished experiments with very small wounds and observations with mosaic apically constricting cells indicate that the response can be to the force generated within the single cell scale or even at the subcellular level. In our study, we used large scale mechanical cues to estimate how far the mechanical signal can reach in the embryo.

 

  1. What do you think the ultimate role of the enrichment of the ADIP-Diversin complex is? You suggest that the enrichment towards the wound edges could trigger a pathway to instruct cell behaviors, and I was wondering if you could expand on what those behaviors might be. Alternatively, considering the observed defects in F-actin and adherens junctions when the complex fails to accumulate, could the enrichment also serve more of a structural role, such as stabilizing junctions to support tension-bearing?

This is a great question to which we do not know the answer.  Based on the known function of ADIP in organizing microtubules, we can speculate that the localization of the protein complex to a particular cell vertex may organize oriented microtubule growth, polarized actomyosin network and/or directional vesicular trafficking. This might be needed for cell shape changes during morphogenesis, junction remodeling allowing cell intercalations or could strengthen cell junctions to resist the force.

 

  1. I find it fascinating that Afadin can interact with ADIP but doesn’t seem to undergo the same polarization of ADIP following wounding, do you have any ideas in which other contexts the interaction Afadin-ADIP can be relevant and required?

We feel that you just formulated an important missing piece to the puzzle of how the ADIP complex works.  Given that Afadin is normally enriched at the very junction, to which the ADIP complex is targeted, the two proteins are likely to interact at some point. Perhaps, only a small fraction of ADIP molecules are activated and delivered to the cell junction, while the rest of overexpressed ADIP molecules are unable to fit there and have to stay in the form of  cytoplasmic condensates.  Notably, Drosophila Afadin/Canoe has been shown to redistribute from bicellular to tricellular junctions during the wound response (Rothenberg et al., 2023).

 

  1. You showed that ADIP depletion leads to impaired wound closure and reduced E-Cadherin and F-actin levels. Have you looked at whether the same defects occur with the ADIP mutant lacking the α-Actinin-binding domain? Since knockdown would disrupt both α-Actinin and Afadin interactions, I wonder if the observed phenotypes could result from loss of those interactions broadly, rather than from the loss of ADIP’s polarization per se.

Correct. We cannot conclude that these defects result from the loss of ADIP polarization. A similar problem exists in the planar polarity field in general. Genetic studies revealed important roles of polarized molecules, yet we are not able to prove that they only function in the specific cellular locations in the cell.  We hope to address this question in our future studies.

 

Reference: Rothenberg KE, Chen Y, McDonald JA, Fernandez-Gonzalez R. Rap1 coordinates cell-cell adhesion and cytoskeletal reorganization to drive collective cell migration in vivo. 2023. Curr Biol. 33(13):2587-2601.

Have your say

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

This site uses Akismet to reduce spam. Learn how your comment data is processed.

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

Register here

Also in the cell biology category:

The essential role of connective-tissue cells during axolotl limb regeneration

Damián García-García, Dunja Knapp, Minjoo Kim, et al.

Selected by 26 June 2025

Dhanuush Balakannan

Developmental Biology

Succinate Dehydrogenase loss causes cascading metabolic effects that impair pyrimidine biosynthesis

Madeleine L. Hart, Kristian Davidsen, Serwah Danquah, et al.

Selected by 26 May 2025

Hannah Pletcher

Cancer Biology

Early resident NK cell response to local HIV infection in lymphoid tissue

David Perea, Alba Gonzalez, Nerea Sanchez-Gaona, et al.

Selected by 19 May 2025

Sukirti Shivpuri et al.

Immunology

preLists in the cell biology category:

June in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: (1) Cell organelles and organisation (2) Cell signaling and mechanosensation (3) Genetics/gene expression (4) Biochemistry (5) Cytoskeleton

 



List by Barbora Knotkova et al.

May in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) Biochemistry/metabolism 2) Cancer cell Biology 3) Cell adhesion, migration and cytoskeleton 4) Cell organelles and organisation 5) Cell signalling and 6) Genetics

 



List by Barbora Knotkova et al.

Keystone Symposium – Metabolic and Nutritional Control of Development and Cell Fate

This preList contains preprints discussed during the Metabolic and Nutritional Control of Development and Cell Fate Keystone Symposia. This conference was organized by Lydia Finley and Ralph J. DeBerardinis and held in the Wylie Center and Tupper Manor at Endicott College, Beverly, MA, United States from May 7th to 9th 2025. This meeting marked the first in-person gathering of leading researchers exploring how metabolism influences development, including processes like cell fate, tissue patterning, and organ function, through nutrient availability and metabolic regulation. By integrating modern metabolic tools with genetic and epidemiological insights across model organisms, this event highlighted key mechanisms and identified open questions to advance the emerging field of developmental metabolism.

 



List by Virginia Savy, Martin Estermann

April in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry/metabolism 2) cell cycle and division 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) (epi)genetics

 



List by Vibha SINGH et al.

March in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) cancer biology 2) cell migration 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) genetics and genomics 6) other

 



List by Girish Kale et al.

Biologists @ 100 conference preList

This preList aims to capture all preprints being discussed at the Biologists @100 conference in Liverpool, UK, either as part of the poster sessions or the (flash/short/full-length) talks.

 



List by Reinier Prosee, Jonathan Townson

February in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry and cell metabolism 2) cell organelles and organisation 3) cell signalling, migration and mechanosensing

 



List by Barbora Knotkova et al.

Community-driven preList – Immunology

In this community-driven preList, a group of preLighters, with expertise in different areas of immunology have worked together to create this preprint reading list.

 



List by Felipe Del Valle Batalla et al.

January in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry/metabolism 2) cell migration 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) genetics/gene expression

 



List by Barbora Knotkova et al.

December in preprints – the CellBio edition

A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) cell cycle and division 2) cell migration and cytoskeleton 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) genetics/gene expression

 



List by Matthew Davies et al.

November in preprints – the CellBio edition

This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression

 



List by Felipe Del Valle Batalla et al.

BSCB-Biochemical Society 2024 Cell Migration meeting

This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.

 



List by Reinier Prosee

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria

 



List by Dey Lab, Samantha Seah

1

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

MitoList

This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.

 



List by Sandra Franco Iborra

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA

 



List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.

 



List by Dey Lab, Amanda Haage