Shaye Daniel D, Casanova Jordi, Llimargas Marta
Institut de Biologia Molecular de Barcelona-CSIC, C/Baldiri Reixac 10, 08028 Barcelona, Spain.
Nat Cell Biol. 2008 Aug;10(8):964-70. doi: 10.1038/ncb1756. Epub 2008 Jul 20.
Through intercalation, a fundamental mechanism underlying elongation during morphogenesis, epithelial cells exchange places in a spatially oriented manner. Epithelial cells are tightly coupled through distinct intercellular junctions, including adherens junctions. Whether trafficking-mediated regulation of adhesion through adherens junctions modulates intercalation in vivo remains controversial. In Drosophila melanogaster, cells in most branches intercalate during tracheal development. However, Wingless (Wg)-promoted expression of the transcription factor Spalt (Sal) in the dorsal trunk inhibits intercalation by an unknown mechanism. Here we have examined the role of trafficking in tracheal intercalation and show that it requires endocytosis, whereas it is opposed by Rab11-mediated recycling in the dorsal trunk. Subapical Rab11 accumulation is enhanced by sal and elevated Rab11-mediated recycling occurs in the dorsal trunk, suggesting that upregulation of Rab11 is one way in which sal inhibits intercalation. We found that dRip11, which regulates Rab11 localization and function, is regulated by sal and can modulate intercalation. Finally, we provide evidence that levels of E-cadherin (DE-cad), an adherens junction component and Rab11-compartment cargo, are dynamically regulated by trafficking during tracheal development, and that such regulation modulates intercalation. Our work suggests a mechanism by which trafficking of adhesion molecules regulates intercalation, and shows how this mechanism can be modulated in vivo to influence cell behaviour.
通过嵌入(形态发生过程中伸长的一种基本机制),上皮细胞以空间定向的方式交换位置。上皮细胞通过包括黏着连接在内的不同细胞间连接紧密相连。通过黏着连接进行的运输介导的黏附调节是否在体内调节嵌入仍存在争议。在黑腹果蝇中,气管发育过程中大多数分支中的细胞会发生嵌入。然而,无翅(Wg)促进转录因子Spalt(Sal)在背干中的表达,通过未知机制抑制嵌入。在这里,我们研究了运输在气管嵌入中的作用,发现它需要内吞作用,而在背干中它受到Rab11介导的再循环的抑制。Sal增强了顶端下Rab11的积累,并且在背干中发生了Rab11介导的再循环增加,这表明Rab11的上调是Sal抑制嵌入的一种方式。我们发现调节Rab11定位和功能的dRip11受Sal调节并能调节嵌入。最后,我们提供证据表明,作为黏着连接成分和Rab11区室货物的E-钙黏蛋白(DE-cad)水平在气管发育过程中通过运输动态调节,并且这种调节调节嵌入。我们的工作提出了一种黏附分子运输调节嵌入的机制,并展示了这种机制在体内如何被调节以影响细胞行为。