Abstract:
Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.
摘要:
心脏发育是一个微妙而复杂的过程,由各种信号通路的协调调节。在这项研究中,我们通过调节Wnt/β-Catenin信号通路研究了sox18在心脏发育中的作用。我们的时空表达分析表明,sox18主要在心脏中表达,branch弓,咽弓,脊髓,和热带非洲爪狼胚胎尾芽期的节间血管。Sox18在热带X胚胎中的过表达会导致心脏水肿,而sox18的功能丧失可以在不同阶段改变发育心脏标志物gata4的信号,这表明sox18在心脏发育中起着至关重要的作用。SOX18在人脐静脉内皮细胞中的敲除表明Sox18与β-CATENIN之间存在联系,Wnt信号通路的关键调节因子。Sox18负调节islet1和tbx3,Wnt/β-Catenin信号的下游因子,在线性心脏管形成和心脏循环阶段。一起来看,我们的发现强调了Sox18通过抑制Wnt/β-Catenin信号在心脏发育中的关键作用。