期刊
EMBO JOURNAL
卷 41, 期 24, 页码 -出版社
WILEY
DOI: 10.15252/embj.2022111021
关键词
AMIS; apical-basal polarity; cadherin; de novo polarisation; epithelial tube
资金
- Wellcome Trust [208758/Z/17/Z, DH160086, 207415/Z/17/Z]
- Royal Society [208758/Z/17/Z, DH160086]
- European Union [844330]
- Issac Newton Trust [ECF-2019-175]
- Leverhulme Trust [ECF-2019-175]
- ERC [669198]
- Marie Curie Actions (MSCA) [844330] Funding Source: Marie Curie Actions (MSCA)
- Wellcome Trust [208758/Z/17/Z] Funding Source: Wellcome Trust
- European Research Council (ERC) [669198] Funding Source: European Research Council (ERC)
In the process of polarization, individual cells must integrate their forming apical domains into a central apical membrane initiation site (AMIS). Cell adhesion and cell division are two interrelated mechanisms of apical polarity localization, which work together to ensure the orderly formation of lumens within tissues.
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.
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