Moreno-Fortuny Artal, Bragg Laricia, Cossu Giulio, Roostalu Urmas
Manchester Academic Health Science Centre, Division of Extracellular Matrix and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK.
Manchester Academic Health Science Centre, Division of Extracellular Matrix and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK
Biol Open. 2017 Nov 15;6(11):1592-1601. doi: 10.1242/bio.027771.
Cell polarity has a fundamental role in shaping the morphology of cells and growing tissues. Polarity is commonly thought to be established in response to extracellular signals. Here we used a minimal assay that enabled us to monitor the determination of cell polarity in myogenic and chondrogenic differentiation in the absence of external signalling gradients. We demonstrate that the initiation of cell polarity is regulated by melanoma cell adhesion molecule (MCAM). We found highly polarized localization of MCAM, Moesin (MSN), Scribble (SCRIB) and Van-Gogh-like 2 (VANGL2) at the distal end of elongating myotubes. Knockout of MCAM or elimination of its endocytosis motif does not impair the initiation of myogenesis or myoblast fusion, but prevents myotube elongation. MSN, SCRIB and VANGL2 remain uniformly distributed in MCAM knockout cells. We show that MCAM is also required at early stages of chondrogenic differentiation. In both myogenic and chondrogenic differentiation MCAM knockout leads to transcriptional downregulation of and enhanced MAP kinase activity. Our data demonstrates the importance of cell autonomous polarity in differentiation.
细胞极性在塑造细胞和生长组织的形态方面具有重要作用。通常认为极性是在对细胞外信号的响应中建立的。在这里，我们使用了一种简单的检测方法，使我们能够在没有外部信号梯度的情况下监测成肌和成软骨分化过程中细胞极性的确定。我们证明细胞极性的起始受黑色素瘤细胞粘附分子（MCAM）调控。我们发现MCAM、埃兹蛋白（MSN）、scribble蛋白（SCRIB）和类原钙粘蛋白2（VANGL2）在伸长的肌管远端高度极化定位。敲除MCAM或去除其胞吞基序不会损害成肌的起始或成肌细胞融合，但会阻止肌管伸长。MSN、SCRIB和VANGL2在MCAM敲除细胞中仍均匀分布。我们表明，在软骨形成分化的早期阶段也需要MCAM。在成肌和成软骨分化过程中，MCAM敲除都会导致转录下调并增强丝裂原活化蛋白激酶活性。我们的数据证明了细胞自主极性在分化中的重要性。
