Mandal Amrita, Holowiecki Andrew, Song Yuntao Charlie, Waxman Joshua S
Heart Institute, Molecular Cardiovascular Biology Division, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Molecular and Developmental Biology Graduate Program, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45208, USA.
Heart Institute, Molecular Cardiovascular Biology Division, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Mech Dev. 2017 Feb;143:32-41. doi: 10.1016/j.mod.2017.01.003. Epub 2017 Jan 10.
Canonical Wnt/β-catenin (Wnt) signaling plays multiple conserved roles during fate specification of cardiac progenitors in developing vertebrate embryos. Although lineage analysis in ascidians and mice has indicated there is a close relationship between the cardiac second heart field (SHF) and pharyngeal muscle (PM) progenitors, the signals underlying directional fate decisions of the cells within the cardio-pharyngeal muscle field in vertebrates are not yet understood. Here, we examined the temporal requirements of Wnt signaling in cardiac and PM development. In contrast to a previous report in chicken embryos that suggested Wnt inhibits PM development during somitogenesis, we find that in zebrafish embryos Wnt signaling is sufficient to repress PM development during anterior-posterior patterning. Importantly, the temporal sensitivity of dorso-anterior PMs to increased Wnt signaling largely overlaps with when Wnt signaling promotes specification of the adjacent cardiac progenitors. Furthermore, we find that excess early Wnt signaling can cell autonomously promote expansion of the first heart field (FHF) progenitors at the expense of PM and SHF within the anterior lateral plate mesoderm (ALPM). Our study provides insight into an antagonistic developmental mechanism that balances the sizes of the adjacent cardiac and PM progenitor fields in early vertebrate embryos.
经典Wnt/β-连环蛋白(Wnt)信号通路在脊椎动物胚胎发育过程中心脏祖细胞的命运决定中发挥多种保守作用。尽管对海鞘和小鼠的谱系分析表明心脏第二心脏场(SHF)和咽肌(PM)祖细胞之间存在密切关系,但脊椎动物心咽肌场中细胞定向命运决定的潜在信号仍不清楚。在这里,我们研究了Wnt信号通路在心脏和PM发育中的时间需求。与之前关于鸡胚的一份报告不同,该报告表明Wnt在体节形成过程中抑制PM发育,我们发现在斑马鱼胚胎中,Wnt信号通路足以在前后模式形成过程中抑制PM发育。重要的是,背前部PM对增加的Wnt信号的时间敏感性与Wnt信号促进相邻心脏祖细胞特化的时间基本重叠。此外,我们发现过量的早期Wnt信号可以以牺牲前外侧板中胚层(ALPM)内的PM和SHF为代价,自主促进第一心脏场(FHF)祖细胞的扩增。我们的研究揭示了一种拮抗的发育机制,该机制在早期脊椎动物胚胎中平衡相邻心脏和PM祖细胞场的大小。