Evolution of embryonic polarity: The role of the Wnt signaling pathways

导致胚层起源的发育机制的进化是一个重要的悬而未决的问题。对这个问题的洞察将来自于了解古代动物(如蛇形动物)的生殖层分离。PI一直在利用线虫通过研究动物-植物(AV)轴的规范和进化来洞察生殖层的进化，AV轴是大多数动物卵中发现的基本极性。发育信息沿这一轴的不对称分布对于许多物种的生殖层分离是至关重要的，但其分子基础尚不清楚。PI表明，在线虫中，生殖层分离是通过选择性激活动物极源卵裂球中进化上保守的Wnt/β-catenin途径来介导的。PI还表明，在未来的内胚层中，典型的Wnt信号的激活是由Dsh蛋白介导的，该蛋白定位于鸡蛋的动物极点。在胚胎发育过程中，Dsh mRNA在全球范围内表达，但由于其在外胚层的选择性失稳，该蛋白在内胚层中丰富。了解Dsh在线虫卵和胚胎中是如何调控的，可能有助于深入了解导致AV轴和胚层进化的机制。在这项研究中，PI将使用功能分子方法来阐明1)限制Dsh对内皮细胞激活和稳定的分子机制；2)确定Dsh是否调节发育过程中的肠道形态发生；3)确定斜视是否具有限制内胚层Dsh活性的作用。斜视已被证明在脊椎动物中拮抗经典的Wnt信号，并定位于线虫卵中。总而言之，这些研究可能会为我们提供对动物进化中最神秘的事件之一的洞察。拟议的工作将涉及在科学方面代表性不足的群体的研究生和本科生，这项研究的结果将被纳入国际学生联合会教授的研究生和本科生班级

The evolution of developmental mechanisms that led to the origin of germ layers is an important unsolved question. Insight into this question will come from understanding germ layer segregation in ancient animals such as cnidarians. The PI has been using the cnidarian Nematostella vectensis to gain insight into germ layer evolution by studying the specification and evolution of the animal-vegetal (AV) axis, a fundamental polarity found in most animal eggs. Developmental information asymmetrically distributed along this axis is crucial for germ layer segregation in many species, but its molecular basis is poorly understood. The PI has shown that in Nematostella, germ layer segregation is mediated by selective activation of the evolutionarily conserved Wnt/beta-catenin pathway in animal pole-derived blastomeres. The PI has also shown that the activation of canonical Wnt signaling in future endoderm is mediated by the Dishevelled (Dsh) protein, which is localized to the egg's animal pole. During embryogenesis Dsh mRNA is expressed globally but the protein is enriched in endoderm by its selective destabilization in ectoderm. Understanding how Dsh is regulated in Nematostella eggs and embryos may provide insight into mechanisms that led to evolution of the AV axis and the germ layers. In this research, the PI will use functional molecular approaches to elucidate 1) the molecular mechanisms that restrict Dsh activation and stability to endodermal cells in Nematostella; 2) determine if Dsh regulates gut morphogenesis during development and 3) determine if Strabismus, which has been shown to antagonize canonical Wnt signaling in vertebrates, and is localized in Nematostella eggs has a role in restricting Dsh activity to endoderm. Together, these studies are likely to provide insight into one of the most mysterious events in animal evolution. The proposed work will involve graduate and undergraduate students from groups under-represented in science, and results of this research will be incorporated into graduate and undergraduate classes taught by the PI