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.

脊索定义了发育过程中所有脊椎动物的轴向结构。Notogenesis是中胚层中主要细胞重组，轴向细胞的收敛和扩展的结果。但是，目前尚不完全了解在脊索形成过程中这些过程如何协同作用。脊索前板是尾随脊索板细胞之前的中胚层中的活跃迁移细胞群。我们显示前庭板细胞表达原钙粘蛋白18a（Pcdh18a），钙粘蛋白超家族的成员。我们发现，Pcdh18a介导的E-钙粘着蛋白粘附复合物的再循环将前庭板细胞转化为内聚和快速迁移的细胞群。反过来，前房板细胞随后指示尾随中胚层。我们使用基于网格的数学框架模拟了中胚层早期形成过程中的细胞迁移，并预测对前部局部活动性细胞簇的需求可以指导后部轴向细胞的插入和扩展。确实，嫁接实验验证了这一预测，并且局部Pcdh18a表达诱导了异位的前房室板状细胞群向动物极的迁移。我们的发现表明，Pcdh18a对于弦前板形成很重要，它通过协调脊索的形态发生影响尾随的中胚层细胞表层。嫁接实验验证了这一预测，并且局部Pcdh18a表达诱导了异位的前房室板状细胞群向动物极的迁移。我们的发现表明，Pcdh18a对于弦前板形成很重要，它通过协调脊索的形态发生影响尾随的中胚层细胞表层。嫁接实验验证了这一预测，并且局部Pcdh18a表达诱导了异位的前房室板状细胞群向动物极的迁移。我们的发现表明，Pcdh18a对于弦前板形成很重要，它通过协调脊索的形态发生影响尾随的中胚层细胞表层。