A functional analysis of the evolution of metazoan cell polarity

所有活细胞都有极性（例如前后，上下），这对它们的正常功能是绝对必要的。 例如，上皮细胞产生“内部”和“外部”屏障，胚胎细胞极性是细胞做出重要决定所必需的。 最近的研究表明，许多相同的分子用于上皮细胞和胚胎细胞的极性。 该基金会在具有简单身体计划的动物中使用比较基因组学和功能基因组学，以发现这些分子如何被部署以产生正常功能的组织。 通过抑制它们的正常分子相互作用，这些发现将对正常成人器官（例如肠道，心脏，肺）的功能以及这些过程中的中断/突变如何导致出生缺陷产生重要影响。 该研究计划还有其他更广泛的影响，例如证明许多不同种类的动物和技术对于了解生命如何“运作”是有用的，以及当地社区成员，包括每年超过5,000名K-12 STEM学生，将接触到维护惠特尼海洋生物科学实验室周围的沿海海洋环境的价值，这些海洋环境为用于此目的的动物提供了家园。该项目测试的假设，在空间部署和相互作用的分子的细胞和组织极性的根本变化是必不可少的动物器官和身体计划的演变。最近的发现表明，在部署的刺胞动物Nematostellavectensis相对于bilaterian物种的胚胎中的Par，cWnt，PCP Wnt信号通路的关键差异表明，原肠胚形成（内中胚层形成）的网站，改变了从动物极栉水母和刺胞动物（即“prebilaterian”）的植物极bilaterian。 此外，在刺胞动物的三功能内中胚层的基因调控网络的变化，引起不同的内胚层和中胚层组织类型的形成负责。 比较和正向功能基因组学方法（包括转基因、mRNA错误表达和CRISPR/Cas9基因组编辑）（三胚层两侧动物最早分支的成员），以及栉水母Mnemiopsis leidyi（早于刺胞动物+两侧动物起源的后生动物分支），这两种动物都可在惠特尼海洋实验室全年获得，将被用来确定负责两侧进化创新的分子变化序列。这些研究将确定在这两个物种的发育过程中，细胞信号传导、细胞骨架和细胞粘附系统在细胞极性调节中的整合。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

All living cells have polarity (e.g. front-back, top-bottom) which is absolutely essential for their normal function. For example, epithelial cells generate "inside" and "outside" barriers and embryonic cell polarity is required for cells to make important decisions on what they are going to give rise to in adult forms. Recent work has shown that many of the same molecules are used in both epithelial and embryonic cell polarity. This grant uses both comparative and functional genomics in animals with simple body plans to discover how these molecules are deployed to give rise to normal functioning tissues. By inhibiting their normal molecular interactions these findings will have important implications for how normal adult organs function (e.g. gut, heart, lung) and how disruptions/mutations in these processes give rise to birth defects. The research plan has other broader impacts such as demonstrating that many different kinds of animals and techniques are useful for understanding how life "works" and that local community members, including over 5,000 K-12 STEM students per year, will be exposed to the value of the maintaining coastal marine environments surrounding the Whitney Lab for Marine Bioscience that provide homes for the animals utilized for this research.This project tests the hypothesis that fundamental changes in the spatial deployment and interactions of molecules underlying both cellular and tissue polarity were essential for animal organ and body plan evolution. Recent discoveries showing crucial differences in the deployment of Par, cWnt, and PCP Wnt signaling pathways in embryos of the cnidarian Nematostellla vectensis relative to bilaterian species suggest that the site of gastrulation (endomesoderm formation), changed from the animal pole in ctenophores and cnidarians (i.e. "prebilaterians") to the vegetal pole in bilaterians. Furthermore, changes in the gene regulatory network that give rise to the trifunctional endomesoderm in cnidarians were responsible for the formation of distinct endodermal and mesodermal tissue types. Comparative and forward functional genomic approaches (including transgenesis, mRNA misexpression and CRISPR/Cas9 genome editing) utilizing embryos of the acoel flatworm Hofstenia miamia (a member of the earliest branching clade of triploblastic bilaterians), and the ctenophore Mnemiopsis leidyi (a metazoan clade predating the origin of cnidarians + bilaterians), both available year round at the Whitney Marine Lab, will be used to determine the sequence of molecular changes responsible for bilaterian evolutionary innovations. These studies will determine the integration between cell signaling, the cytoskeleton, and cell adhesion systems in the regulation of cell polarity during the developmental process of these two species.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.