Mesenchymal-to-epithelial transition of intercalating cells in Drosophila renal tubules depends on polarity cues from epithelial neighbours.

Mesenchymal-to-epithelial transition of intercalating cells in Drosophila renal tubules depends on polarity cues from epithelial neighbours.
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DOI:
10.1016/j.mod.2010.04.002
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发表时间:
2010-07
影响因子:
2.6
通讯作者:
Skaer, Helen
Skaer, Helen
中科院分区:
生物学4区
文献类型:
--
作者:
Campbell, Kyra;Casanova, Jordi;Skaer, Helen

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间充质细胞通过间充质-上皮转化(MET)嵌入上皮中,是器官发生(例如,在肾发生中)和组织再生(在细胞更新和伤口修复期间)的基础。尽管它的重要性,令人惊讶的是,很少有人知道的机制,使MET相比,相关的和大量研究,反向过程,上皮细胞间质转化(EMT)。我们分析了调节MET的分子事件,因为星状细胞整合到果蝇发育中的肾小管的既定上皮细胞中。我们发现,星状细胞极化,因为他们整合上皮主细胞和细胞极性蛋白在主细胞中的正常,局部表达所需的星状细胞成为上皮。虽然基底外侧膜和顶膜作为星状细胞极性的线索,但需要粘附连接的完整性来调节它们通过上皮的运动;在没有这些连接的情况下,星状细胞继续迁移到小管腔中。我们还表明,在星状细胞基底外侧蛋白的表达是一个先决条件,他们的主细胞之间的侵入。我们提出了一个模型,在该模型中,与连续的主细胞膜结构域的星状细胞,因为它们之间的整合作为一个线索,星状细胞极性的制定。我们认为,新的细胞邻居之间的粘连小带连接的形成建立了他们的顶端-基底的位置,并稳定他们在上皮。
The intercalation of mesenchymal cells into epithelia, through mesenchymal-to-epithelial transition (MET), underlies organogenesis, for example, in nephrogenesis, and tissue regeneration, during cell renewal and wound repair. Despite its importance, surprisingly little is known about the mechanisms that bring about MET in comparison with the related and much-studied, reverse process, epithelial-to-mesenchymal transition (EMT). We analyse the molecular events that regulate MET as stellate cells integrate into the established epithelium of the developing renal tubules in Drosophila. We show that stellate cells polarise as they integrate between epithelial principal cells and that the normal, localised expression of cell polarity proteins in principal cells is required for stellate cells to become epithelial. While the basolateral and apical membranes act as cues for stellate cell polarity, adherens junction integrity is required to regulate their movement through the epithelium; in the absence of these junctions stellate cells continue migrating into the tubule lumen. We also show that expression of basolateral proteins in stellate cells is a prerequisite for their ingression between principal cells. We present a model in which the contacts with successive principal cell membrane domains made by stellate cells as they integrate between them act as a cue for the elaboration of stellate cell polarity. We suggest that the formation of zonula adherens junctions between new cell neighbours establishes their apico-basal positions and stabilises them in the epithelium.
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