Morphogenetic mechanisms of epithelial tubulogenesis: MDCK cell polarity is transiently rearranged without loss of cell-cell contact during scatter factor hepatocyte growth factor-induced tubulogenesis
Morphogenetic mechanisms of epithelial tubulogenesis: MDCK cell polarity is transiently rearranged without loss of cell-cell contact during scatter factor hepatocyte growth factor-induced tubulogenesis
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DOI：
10.1006/dbio.1998.9091
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发表时间：
1998-12-01
影响因子：
2.7
通讯作者：
Mostov, KE
中科院分区：
文献类型：
--
作者：
Pollack, AL;Runyan, RB;Mostov, KE
许多器官系统是由上皮管网络组成的。最近，诱导上皮小管发育和调节分支位点的分子已被鉴定。然而，很少有人知道的机制，调控细胞重排是必要的小管形成。在这项研究中，我们使用了一个分散因子/肝细胞生长因子诱导的模型系统的MDCK上皮细胞小管形成的细胞重排过程中小管发育的机制进行了分析。我们研究了动态的细胞极性和细胞间连接在小管形成过程中，并提出了证据的多步骤模型，在该模型中，细胞重新排列，而不损失细胞间的接触和小管管腔从头形成。顶端和基底侧膜亚域的标记物的三维分析表明，上皮细胞极性是短暂的损失，随后在tubulogenesis恢复。此外，细胞-细胞连接复合物的组分经历深刻的重排：E-钙粘蛋白随机分布在细胞表面周围，桥斑蛋白I/II在细胞内积累，紧密连接蛋白ZO-1仍然定位在细胞-细胞接触的位点。这表明细胞-细胞连接的差异调节对于小管的形成是重要的。因此，在微管形成过程中，细胞-细胞粘附接触受到差异调节，而质膜亚结构域的极性和特化重组，使细胞在重新排列成新结构时保持接触。(C)北京：科学出版社.
Many organ systems are composed of networks of epithelial tubes. Recently, molecules that induce development of epithelial tubules and regulate sites of branching have been identified. However, little is known about the mechanisms regulating cell rearrangements that are necessary for tubule formation. In this study we have used a scatter factor/hepatocyte growth factor-induced model system of MDCK epithelial cell tubulogenesis to analyze the mechanisms of cell rearrangement during tubule development. We examined the dynamics of cell polarity and cell-cell junctions during tubule formation and present evidence for a multistep model of tubulogenesis in which cells rearrange without loss of cell-cell contacts and tubule lumens form de novo. A three-dimensional analysis of markers for apical and basolateral membrane subdomains shows that epithelial cell polarity is transiently lost and subsequently regained during tubulogenesis. Furthermore, components of cell-cell junctional complexes undergo profound rearrangements: E-cadherin is randomly distributed around the cell surface, desmoplakins I/II accumulate intracellularly, and the tight junction protein ZO-1 remains localized at sites of cell-cell contact. This suggests that differential regulation of cell-cell junctions is important for the formation of tubules. Therefore, during tubulogenesis, cell-cell adhesive contacts are differentially regulated while the polarity and specialization of plasma membrane subdomains reorganize, enabling cells to remain in contact as they rearrange into new structures. (C) 1998 Academic Press.