Institute of Biochemistry and Biology, Potsdam University, D-14476 Potsdam, Germany.
Development. 2023 Sep 15;150(18). doi: 10.1242/dev.201707. Epub 2023 Sep 25.
During zebrafish heart formation, cardiac progenitor cells converge at the embryonic midline where they form the cardiac cone. Subsequently, this structure transforms into a heart tube. Little is known about the molecular mechanisms that control these morphogenetic processes. Here, we use light-sheet microscopy and combine genetic, molecular biological and pharmacological tools to show that the paralogous genes wnt9a/b are required for the assembly of the nascent heart tube. In wnt9a/b double mutants, cardiomyocyte progenitor cells are delayed in their convergence towards the embryonic midline, the formation of the heart cone is impaired and the transformation into an elongated heart tube fails. The same cardiac phenotype occurs when both canonical and non-canonical Wnt signaling pathways are simultaneously blocked by pharmacological inhibition. This demonstrates that Wnt9a/b and canonical and non-canonical Wnt signaling regulate the migration of cardiomyocyte progenitor cells and control the formation of the cardiac tube. This can be partly attributed to their regulation of the timing of cardiac progenitor cell differentiation. Our study demonstrates how these morphogens activate a combination of downstream pathways to direct cardiac morphogenesis.
在斑马鱼心脏形成过程中，心脏祖细胞汇聚在胚胎的中线上，在那里它们形成心脏锥。随后，这个结构转变成一个心脏管。关于控制这些形态发生过程的分子机制知之甚少。在这里，我们使用光片显微镜，并结合遗传、分子生物学和药理学工具，表明旁系基因 wnt9a/b 对于新生心脏管的组装是必需的。在 wnt9a/b 双突变体中，心肌细胞祖细胞在向胚胎中线的汇聚中延迟，心脏锥的形成受损，并且不能转化为伸长的心脏管。当同时通过药理学抑制阻断经典和非经典 Wnt 信号通路时，会出现相同的心脏表型。这表明 Wnt9a/b 和经典和非经典 Wnt 信号调节心肌细胞祖细胞的迁移，并控制心脏管的形成。这部分归因于它们对心脏祖细胞分化时间的调节。我们的研究表明这些形态发生素如何激活下游途径的组合来指导心脏形态发生。
