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E-cadherin mediated Apical Membrane Initiation Site localisation

Liang, Xuan and Weberling, Antonia and Hii, Chun Yuan and Zernicka-Goetz, Magdalena and Buckley, Clare E. (2021) E-cadherin mediated Apical Membrane Initiation Site localisation. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20211214-786549900

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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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.11.30.470571DOIDiscussion Paper
https://github.com/Buckley-Lab-opto/Liang-2022Related ItemCode
https://resolver.caltech.edu/CaltechAUTHORS:20220826-428674800Related ItemJournal Article
ORCID:
AuthorORCID
Liang, Xuan0000-0003-4019-1457
Weberling, Antonia0000-0001-8282-5695
Hii, Chun Yuan0000-0002-5344-9747
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Buckley, Clare E.0000-0003-3329-3973
Alternate Title:CADHERIN mediated AMIS localisation, E-cadherin mediated AMIS localisation
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-2022
Funders:
Funding AgencyGrant Number
Wellcome Trust208758/Z/17/Z
Royal SocietyDH160086
Marie Curie Fellowship844330
Issac Newton TrustUNSPECIFIED
Leverhulme TrustECF-2019-175
Wellcome Trust207415/Z/17/Z
European Research Council (ERC)669198
Subject Keywords:AMIS/Cadherin/apical-basal polarity/epithelial tube/de novo polarisation
DOI:10.1101/2021.11.30.470571
Record Number:CaltechAUTHORS:20211214-786549900
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20211214-786549900
Official Citation:E-cadherin mediated Apical Membrane Initiation Site localisation. Xuan Liang, Antonia Weberling, Chun Yuan Hii, Magdalena Zernicka-Goetz, Clare E Buckley. bioRxiv 2021.11.30.470571; doi: https://doi.org/10.1101/2021.11.30.470571
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:112398
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 Dec 2021 16:38
Last Modified:31 Aug 2022 15:30

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