The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension
The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension
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DOI：
10.1371/journal.pbio.3000522
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发表时间：
2019-12-01
期刊：
影响因子：
9.8
通讯作者：
Sanson, Benedicte
中科院分区：
文献类型：
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作者：
Finegan, Tara M.;Hervieux, Nathan;Sanson, Benedicte
在上皮细胞中，三细胞顶点正在成为调节上皮完整性和功能的重要部位。然而，与双细胞接触相比，人们所知甚少。特别是，三细胞顶点的常驻蛋白仅在闭塞连接处被识别，而在粘附连接处（AJ）则没有发现。在之前的一项研究中，我们发现，在果蝇胚胎中，粘附分子 Sidekick (Sdk) 在无脊椎动物和脊椎动物中因其在视觉系统中的作用而闻名，定位于 AJ 水平的三细胞顶点。在这里，我们调查了广泛的果蝇上皮细胞，并确定 Sdk 是三细胞 AJ（tAJ）的常驻蛋白，这是此类蛋白中的第一个。克隆分析表明，贡献 Sdk 的两个细胞（而不是三个细胞）足以进行 tAJ 定位。使用结构照明的超分辨率成像揭示了 Sdk 蛋白在顶点形成弦状结构。假设 Sdk 可能在 AJ 主动重塑的上皮细胞中发挥作用，我们使用定量方法分析了果蝇轴延伸过程中 sdk 无效突变体胚胎的表型。我们发现 sdk 突变体的顶端细胞形状异常，表明在收敛和延伸过程中组织重塑存在缺陷。此外，在细胞重新排列过程中，顶端顶点的粘附受到损害，皮质中的顶端撕裂形成并在整个轴延伸过程中持续存在，尤其是在玫瑰花结的中心。最后，我们发现 sdk 突变体中极化细胞嵌入减少。细胞行为的数学模型支持这样的观点，即极化细胞嵌入的 T1 转变在 sdk 突变体中被延迟，特别是在玫瑰花结中。我们认为这种延迟与会聚和延伸组织的机械特性的变化相结合，导致 sdk 突变体胚胎中异常的顶端细胞形状。
In epithelia, tricellular vertices are emerging as important sites for the regulation of epithelial integrity and function. Compared to bicellular contacts, however, much less is known. In particular, resident proteins at tricellular vertices were identified only at occluding junctions, with none known at adherens junctions (AJs). In a previous study, we discovered that in Drosophila embryos, the adhesion molecule Sidekick (Sdk), well-known in invertebrates and vertebrates for its role in the visual system, localises at tricellular vertices at the level of AJs. Here, we survey a wide range of Drosophila epithelia and establish that Sdk is a resident protein at tricellular AJs (tAJs), the first of its kind. Clonal analysis showed that two cells, rather than three cells, contributing Sdk are sufficient for tAJ localisation. Super-resolution imaging using structured illumination reveals that Sdk proteins form string-like structures at vertices. Postulating that Sdk may have a role in epithelia where AJs are actively remodelled, we analysed the phenotype of sdk null mutant embryos during Drosophila axis extension using quantitative methods. We find that apical cell shapes are abnormal in sdk mutants, suggesting a defect in tissue remodelling during convergence and extension. Moreover, adhesion at apical vertices is compromised in rearranging cells, with apical tears in the cortex forming and persisting throughout axis extension, especially at the centres of rosettes. Finally, we show that polarised cell intercalation is decreased in sdk mutants. Mathematical modelling of the cell behaviours supports the notion that the T1 transitions of polarised cell intercalation are delayed in sdk mutants, in particular in rosettes. We propose that this delay, in combination with a change in the mechanical properties of the converging and extending tissue, causes the abnormal apical cell shapes in sdk mutant embryos.