A functional analysis of the evolution of metazoan cell polarity

后生动物细胞极性进化的功能分析

• 批准号: 1755364
• 负责人: Mark Martindale
• 金额: $ 85万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755364&HistoricalAwards=false
• 关键词: functional; analysis; evolution; metazoan; cell

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.

所有活细胞都有极性(例如，前后、顶底)，这对它们的正常功能是绝对必要的。例如，上皮细胞产生“内”和“外”屏障，胚胎细胞的极性是细胞做出重要决定的必要条件，这些决定决定了它们将在成体中产生什么。最近的研究表明，许多相同的分子同时用于上皮细胞和胚胎细胞的极性。这项资助在动物身上同时使用了比较基因组学和功能基因组学，通过简单的身体计划来发现这些分子是如何部署的，以产生正常功能的组织。通过抑制它们正常的分子相互作用，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具有重要意义。该研究计划还有其他更广泛的影响，如展示许多不同种类的动物和技术有助于理解生命是如何工作的，当地社区成员，包括每年超过5,000名K-12 STEM学生，将接触到惠特尼海洋生物科学实验室周围维护的沿海海洋环境的价值，该实验室为用于这项研究的动物提供了家园。该项目测试了一种假设，即细胞和组织极性背后的分子的空间部署和相互作用的根本变化对动物器官和身体计划的进化至关重要。最近的发现表明，与双边物种相比，矢状线虫在胚胎中PAR、cWnt和PCP Wnt信号通路的部署存在重大差异，这表明原肠形成(内胚层形成)的位置从线虫和线虫的动物极(即双侧前动物)转变为双栖动物的植物极。此外，产生三功能内胚层的基因调控网络的变化是形成不同的内胚层和中胚层组织类型的原因。惠特尼海洋实验室常年提供的比较和正向功能基因组方法(包括转基因、mRNA错误表达和CRISPR/Cas9基因组编辑)将被用来确定导致双边进化创新的分子变化序列，这两个方法都是惠特尼海洋实验室常年提供的，利用了扁平线虫Hoftenia miamia(三倍体双边最早分支的成员)和线虫Mnformopsis leidyi(后生动物+双边动物起源之前的后生动物分支)的胚胎。这些研究将确定在这两个物种的发育过程中细胞信号、细胞骨架和细胞黏附系统在细胞极性调节中的整合。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Improved protocol for spawning and immunostaining embryos and juvenile stages of the ctenophore Mnemiopsis leidyi

栉水母 Mnemiopsis leidyi 产卵和免疫染色胚胎和幼年阶段的改进方案

• DOI: 10.1038/protex.2018.092
• 发表时间: 2018
• 期刊: Protocol Exchange
• 作者: Salinas-Saavedra, Miguel;Salinas-Saavedra, Miguel;Martindale, Mark Q.
• 通讯作者: Martindale, Mark Q.

Knockout of a single Sox gene resurrects an ancestral cell type in the sea anemone Nematostella vectensis.

敲除单个 Sox 基因可以使海葵 Nematostella vectensis 的祖先细胞类型复活。

• DOI: 10.1101/2021.09.30.462561
• 发表时间: 2021
• 期刊: bioRxiv
• 作者: Babonis, L.S.

Cellular micromasonry: biofabrication with single cell precision

细胞微砌体：单细胞精度的生物制造

• DOI: 10.1039/d2sm01013e
• 发表时间: 2022
• 期刊: Soft Matter
• 影响因子: 3.4
• 作者: Ellison, S. Tori;Duraivel, Senthilkumar;Subramaniam, Vignesh;Hugosson, Fredrik;Yu, Bo;Lebowitz, Joseph J.;Khoshbouei, Habibeh;Lele, Tanmay P.;Martindale, Mark Q.;Angelini, Thomas E.
• 通讯作者: Angelini, Thomas E.

Par protein localization during the early development of Mnemiopsis leidyi suggests different modes of epithelial organization in the metazoa

Mnemiopsis leidyi 早期发育过程中的 Par 蛋白定位表明后生动物上皮组织的不同模式

• DOI: 10.7554/elife.54927
• 发表时间: 2020
• 期刊: eLife
• 影响因子: 7.7
• 作者: Salinas-Saavedra, Miguel;Martindale, Mark Q
• 通讯作者: Martindale, Mark Q