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E-cadherin mediates apical membrane initiation site localisation during de novo polarisation of epithelial cavities

Liang, Xuan and Weberling, Antonia and Hii, Chun Yuan and Zernicka-Goetz, Magdalena and Buckley, Clare E. (2022) E-cadherin mediates apical membrane initiation site localisation during de novo polarisation of epithelial cavities. EMBO Journal . Art No. e111021. ISSN 0261-4189. doi:10.15252/embj.2022111021. (In Press)

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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 suggests that cell–cell adhesion localises apical proteins such as PAR-6 to a centralised AMIS. Unexpectedly, we also found that mESC 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:Article
Related URLs:
URLURL TypeDescription ItemDiscussion Paper
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:E-cadherin mediated Apical Membrane Initiation Site localisation
Additional Information:We are grateful to Jon Clarke and Ben Steventon for critical reading of the manuscript and other members of the Buckley and Zernicka-Goetz laboratories for scientific discussion, especially Matteo Molè and Marta Shahbazi. Thank you to the Shukry Habib laboratory for kindly gifting the W4 cells and the Lionel Larue laboratory for kindly gifting the Cdh1 KO cells. Thank you to the Cambridge Advanced Imaging Centre and the Ewa Paluch laboratory for help and access to confocal microscopy. 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.
Funding AgencyGrant Number
Wellcome Trust208758/Z/17/Z
Royal SocietyDH160086
European Research Council (ERC)844330
Issac Newton TrustUNSPECIFIED
Leverhulme TrustECF‐2019‐175
Wellcome Trust207415/Z/17/Z
European Research Council (ERC)669198
Record Number:CaltechAUTHORS:20220826-428674800.766
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:116581
Deposited By: Melissa Ray
Deposited On:31 Aug 2022 15:34
Last Modified:06 Dec 2022 23:04

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