E-cadherin mediated Apical Membrane Initiation Site localisation
Abstract
Individual cells within de novo polarising tubes and cavities must integrate their forming apical domains into a centralised apical membrane initiation site (AMIS). This is necessary to enable organised lumen formation within multi-cellular tissue. Despite the well documented importance of cell division in localising the AMIS, we have found a division-independent mechanism of AMIS localisation that relies instead on Cadherin-mediated cell-cell adhesion. Our study of de novo polarising mouse embryonic stem cells (mESCs) cultured in 3D suggest that cell-cell adhesion localises apical proteins such as PAR-6 to a centralised AMIS. Unexpectedly, we also found that mESC cell clusters lacking functional E-cadherin still formed a lumen-like cavity in the absence of AMIS localisation but did so at a later stage of development via a closure mechanism, instead of via hollowing. This work suggests that there are two, interrelated mechanisms of apical polarity localisation: cell adhesion and cell division. Alignment of these mechanisms in space allows for redundancy in the system and ensures the development of a coherent epithelial structure within a growing organ.
Additional Information
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Version 1 - December 1, 2021; Version 2 - December 7, 2021; Version 3 - December 8, 2021; Version 4 - February 25, 2022; Version 5 - June 7, 2022. We are grateful to Jon Clarke and Ben Steventon for critical reading of the manuscript and other members of the Buckley and Zernicka-Goetz labs for scientific discussion, especially Matteo Molè and Marta Shahbazi. Thank you to the Shukry Habib lab for kindly gifting the W4 cells and the Lionel Larue lab for kindly gifting the Cdh1 KO cells. Thank you to the Cambridge Advanced Imaging Centre and the Ewa Paluch lab for help and access to confocal microscopy. Funding: This research was financially supported by: CEB - the Wellcome Trust and Royal Society (Sir Henry Dale Fellowship grant no. 208758/Z/17/Z and Dorothy Hodgkin Fellowship grant no. DH160086), XL - European Union's Horizon 2020 programme (Marie Skłodowska-Curie Individual Fellowship grant no. 844330), the Issac Newton Trust and Leverhulme Trust (Leverhulme Early Career Fellowship grant no. ECF-2019-175). MZG - The Wellcome Trust (207415/Z/17/Z) and ERC (669198). For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. Author contributions: Conceptualisation: CEB, XL. Methodology: XL, CEB, AW. Formal analysis: XL, CYH. Investigation: XL, AW. Writing: CEB, XL. Visualisation: XL. Supervision: CEB, MZG. Funding acquisition: CEB, XL, MZG. The authors declare that they have no conflict of interest. Data and code availability: Image data is accessible in the BioImage Archive, accession number S-BIAD473. The R-language code for generating the PAR-3 heatmap in Figure 5D is accessible at: https://github.com/Buckley-Lab-opto/Liang-2022Attached Files
Submitted - 2021.11.30.470571v5.full.pdf
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Additional details
- Alternative title
- CADHERIN mediated AMIS localisation
- Alternative title
- E-cadherin mediated AMIS localisation
- Eprint ID
- 112398
- Resolver ID
- CaltechAUTHORS:20211214-786549900
- 208758/Z/17/Z
- Wellcome Trust
- DH160086
- Royal Society
- 844330
- Marie Curie Fellowship
- Issac Newton Trust
- ECF-2019-175
- Leverhulme Trust
- 207415/Z/17/Z
- Wellcome Trust
- 669198
- European Research Council (ERC)
- Created
-
2021-12-14Created from EPrint's datestamp field
- Updated
-
2022-08-31Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering