E-cadherin mediates apical membrane initiation site localisation during de novo polarisation of epithelial cavities.
E-cadherin mediates apical membrane initiation site localisation during de novo polarisation of epithelial cavities.
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DOI：
10.15252/embj.2022111021
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发表时间：
2022-12-15
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从头极化管和腔中的单个细胞必须将其形成的顶端结构域整合到集中的顶端膜起始位点（AMIS）中。这对于在多细胞组织内形成有组织的管腔是必要的。尽管细胞分裂在AMIS定位中的重要性得到了充分的证明，但我们已经发现了AMIS定位的不依赖于分裂的机制，该机制依赖于钙粘蛋白介导的细胞-细胞粘附。我们对3D培养的小鼠胚胎干细胞（mESC）重新极化的研究表明，细胞-细胞粘附将顶端蛋白（如PAR-6）定位于集中的AMIS。出乎意料的是，我们还发现缺乏功能性E-钙粘蛋白的mESC簇在没有AMIS定位的情况下仍然形成管腔样空腔，但在发育的后期通过“闭合”机制而不是通过中空化。这项工作表明，有两个相互关联的机制顶端极性定位：细胞粘附和细胞分裂。这些机制在空间上的对齐允许系统中的冗余，并确保生长器官内连贯的上皮结构的发育。在胚胎干细胞的上皮极化过程中，顶膜起始的位点由E-钙粘蛋白介导的细胞粘附决定，与细胞分裂无关。
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. During epithelial polarisation of embryonic stem cells, the site of apical membrane initiation is defined by E‐cadherin‐mediated cell adhesion independently of cell division.
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