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尚未解决的重要问题。对这个问题的深入了解将来自于对刺胞动物等古代动物的胚层分离的了解。 PI 一直在利用刺胞动物 Nematostella vectensis 通过研究动植物 (AV) 轴（大多数动物卵中发现的基本极性）的规范和进化来深入了解胚层进化。沿该轴不对称分布的发育信息对于许多物种的胚层分离至关重要，但其分子基础却知之甚少。 PI 表明，在 Nematostella 中，胚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 途径介导的。 PI 还表明，未来内胚层中经典 Wnt 信号传导的激活是由位于卵子动物极的 Disheveled (Dsh) 蛋白介导的。在胚胎发生过程中，Dsh mRNA 全面表达，但该蛋白质通过其在外胚层中的选择性去稳定而在内胚层中富集。了解 Dsh 在线虫卵和胚胎中的调控方式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) 限制线虫内胚层细胞 Dsh 激活和稳定性的分子机制； 2) 确定 Dsh 是否在发育过程中调节肠道形态发生；3) 确定斜视（已被证明可以拮抗脊椎动物中的经典 Wnt 信号传导，并且位于线虫卵中）是否具有限制内胚层 Dsh 活性的作用。总之，这些研究可能会深入了解动物进化中最神秘的事件之一。拟议的工作将涉及科学领域代表性不足的群体的研究生和本科生，这项研究的结果将纳入 PI 教授的研究生和本科生课程中

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