PDF(Pubmed)
Abstract：
Asymmetric vertebrate heart development is driven by an intricate sequence of morphogenetic cell movements, the coordination of which requires precise interpretation of signaling cues by heart primordia. Here we show that Nodal functions cooperatively with FGF during heart tube formation and asymmetric placement. Both pathways act as migratory stimuli for cardiac progenitor cells (CPCs), but FGF is dispensable for directing heart tube asymmetry, which is governed by Nodal. We further find that Nodal controls CPC migration by inducing left-right asymmetries in the formation of actin-based protrusions in CPCs. Additionally, we define a developmental window in which FGF signals are required for proper heart looping and show cooperativity between FGF and Nodal in this process. We present evidence FGF may promote heart looping through addition of the secondary heart field. Finally, we demonstrate that loss of FGF signaling affects proper development of the atrioventricular canal (AVC), which likely contributes to abnormal chamber morphologies in FGF-deficient hearts. Together, our data shed insight into how the spatiotemporal dynamics of signaling cues regulate the cellular behaviors underlying organ morphogenesis.
摘要：
不对称脊椎动物心脏发育是由一系列复杂的形态发生细胞运动驱动的，其协调需要心脏原基对信号线索的精确解释。在这里，我们表明Nodal在心脏管形成和不对称放置期间与FGF协同作用。这两种途径都作为心脏祖细胞（CPCs）的迁移刺激，但是FGF对于指导心脏导管不对称是可有可无的，由节点管理。我们进一步发现，Nodal通过在CPC中基于肌动蛋白的突起的形成中诱导左右不对称性来控制CPC迁移。此外,我们定义了一个发育窗口，在该窗口中，FGF信号是正确的心脏循环所必需的，并且在此过程中显示了FGF和Nodal之间的协同作用。我们提供证据，FGF可能通过增加次级心脏区域来促进心脏循环。最后,我们证明FGF信号的丢失会影响房室管（AVC）的正常发育，这可能有助于FGF缺乏心脏中异常的腔室形态。一起,我们的数据揭示了信号线索的时空动力学如何调节器官形态发生的细胞行为。
■这项研究探讨了Nodal和FGF信号在产生心脏不对称中的合作和独立作用。
■这项研究探讨了Nodal和FGF信号在产生心脏不对称中的合作和独立作用。
