Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish.

Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish.
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PCDH18A调节斑马鱼轴向中胚层发育期间E-钙粘蛋白的内吞作用。

DOI:
10.1007/s00418-020-01887-5
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发表时间:
2020-11
影响因子:
2.3
通讯作者:
Scholpp S
Scholpp S
中科院分区:
生物学3区
文献类型:
--
作者:
Bosze B;Ono Y;Mattes B;Sinner C;Gourain V;Thumberger T;Tlili S;Wittbrodt J;Saunders TE;Strähle U;Schug A;Scholpp S

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脊索决定了所有脊椎动物在发育过程中的轴向结构。肿瘤发生是中胚层主要细胞重组、轴向细胞汇聚和延伸的结果。然而,目前还不完全了解这些过程如何在脊索形成过程中以协调的方式共同作用。前脊索板是中央中胚层中一个活跃的迁移细胞群,位于尾随脊索板细胞的前面。我们发现脊索前板细胞表达原钙粘蛋白18a(Pcdh18a),它是钙粘蛋白超家族的成员之一。我们发现,Pcdh18a介导的E-钙粘附素黏附复合体的再循环将脊索前板状细胞转变为具有凝聚力和快速迁移的细胞群。反过来,前索板状细胞随后指示尾随的中胚层。我们使用基于网格的数学框架模拟了早期中胚层形成过程中的细胞迁移,并预测对前部局部活动细胞团的要求可以指导后部轴向细胞的插入和伸展。事实上,一项移植实验证实了这一预测,局部表达Pcdh18a诱导了一个异位的前索板状细胞群向动物极部迁移。我们的发现表明,Pcdh18a对于前索的形成是重要的,它通过协调脊索的形态发生来影响拖尾的中胚层细胞膜。本文的在线版本(10.1007/s00418-020-01887-5)包含补充材料,可供授权用户使用。
The notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation. The prechordal plate is an actively migrating cell population in the central mesoderm anterior to the trailing notochordal plate cells. We show that prechordal plate cells express Protocadherin 18a (Pcdh18a), a member of the cadherin superfamily. We find that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms prechordal plate cells into a cohesive and fast migrating cell group. In turn, the prechordal plate cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation and extension of the posterior, axial cells. Indeed, a grafting experiment validated the prediction and local Pcdh18a expression induced an ectopic prechordal plate-like cell group migrating towards the animal pole. Our findings indicate that the Pcdh18a is important for prechordal plate formation, which influences the trailing mesodermal cell sheet by orchestrating the morphogenesis of the notochord. The online version of this article (10.1007/s00418-020-01887-5) contains supplementary material, which is available to authorized users.
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