Multiciliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo
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During embryonic development, regeneration, and homeostasis, cells have to migrate and physically integrate into the target tissues where they ultimately execute their function. While much is known about the biochemical pathways driving cell migration in vivo, we are only beginning to understand the mechanical interplay between migrating cells and their surrounding tissue. Here, we reveal that multiciliated cell precursors in the Xenopus embryo use filopodia to pull at the vertices of the overlying epithelial sheet. This pulling is effectively used to sense vertex stiffness and identify the preferred positions for cell integration into the tissue. Notably, we find that pulling forces equip multiciliated cells with the ability to remodel the epithelial junctions of the neighboring cells, enabling them to generate a permissive environment that facilitates integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 6423 |
| Tidsskrift | Nature Communications |
| Vol/bind | 13 |
| Udgave nummer | 1 |
| Antal sider | 15 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The authors thank all members of the Sedzinski lab and Active & Intelligent Matter Group members for comments and suggestions, Aritra Misra for performing the phospho-myosin stainings, Martin Proks for help in analyzing the laser ablation and phospho-myosin data, Girish Rajendraprasad and Marin Barisic for technical assistance and usage of the laser ablation system, Elke Ober and Mariaceleste Aragona for critical reading of the manuscript, Ann L. Miller, Edwin Munro and Elias H. Barriga for key reagents, and Benoit Aigouy for help with Tissue Analyzer. We acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen and reNEW’s microscopy specialist, Jutta M. Bulkescher, for training, technical expertise, support, and microscope use. J.S. acknowledges the support of the Novo Nordisk Foundation (grant No. NNF19OC0056962) and Leo Foundation (LF-OC-19-000219); A.D. acknowledges the support from the Novo Nordisk Foundation (grant No. NNF18SA0035142), Villum Fonden (Grant no. 29476), and funding from the European Union via ERC Starting Grant PhysCoMeT. A.A. acknowledges support from the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under project 031L0160. The Novo Nordisk Foundation Center for Stem Cell Biology and Novo Nordisk Foundation Center for Stem Cell Medicine are supported by Novo Nordisk Foundation grants (NNF17CC0027852 and NNF21CC0073729).
Publisher Copyright:
© 2022, The Author(s).
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