Gene regulatory network evolution and the origin of biological novelties

基因调控网络进化和生物新颖性的起源

• 批准号: 8667927
• 负责人: MARK q MARTINDALE
• 金额: $ 20.36万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8667927
• 关键词: Gene; regulatory; network; evolution; origin

DESCRIPTION (provided by applicant): Cells acquire their unique fates by the differential pathways of combinatorial gene activity during the developmental period. Gene regulatory networks (GRN) controlling the specification of endomesodermal cell fates have been constructed in a handful of model systems, include sea urchins, vertebrates, and nematodes. Endomesodermal precursors that give rise to endodermal (gut derivatives) and mesodermal (muscle, blood, coelom, kidney and skeletal elements) cell types become distinct from ectodermal precursors (that give rise to epidermis and nervous system) by differential gene expression. Separate endodermal and mesodermal fates are then specified subsequently from endomesodermal precursors. Understanding the relationship between intracellular factors and extracellular signals, and reconstructing gene regulatory networks between different animal species can provide key insights in how and when the molecular and morphological characters of each organism are built. A prime example is the original evolutionary appearance of the mesodermal germ layer in animal evolution. Cnidarians (anemones, corals, and "jellyfish") are an animal group whose adults possess derivatives of only two germ layers, ectoderm and a bifunctional (having both absorptive and contractile functions) gastodermal (gut) layer. Cnidarians are the closest living relatives of other bilaterally symmetrical animals that possess all three germ layers, and compelling molecular, genomic, developmental, and evolutionary evidence exists to demonstrate that the cnidarian gastrodermis is the evolutionary precursor of both endodermal and mesodermal germ layers in all other triploblastic bilaterian animals. Thus, unraveling this cnidarian "endomesodermal" gene regulatory network, will provide necessary insight into how GRN sub circuits have been adopted, rewired or co-opted in various metazoan in order to give rise to novel, modified or specialized endomesodermal features. This grant will functionally reconstruct the gene regulatory network underlying endomesoderm formation in the cnidarian sea anemone Nematostella vectensis, (whose genome has been sequenced by the J.G.I (Dept. Energy), using, QPCR, whole genome microarrays, functional techniques such as pharmaceutical drug treatments, synthetic mRNA misexpression, translation and splice blocking morpholino approaches and cis-regulatory analysis. In addition, we will implement all the obtained data into an already existing gene expression database in order to share our findings with the scientific community. The generation of high quality molecular data from a phylogentically pivotal species for the first time will help explain the differences seen in genes and their regulatory interactions previously identified in bilaterian model systems by polarizing the direction of evolutionary change. PUBLIC HEALTH RELEVANCE: Project Narrative Individual cells in developing animal embryos learn their ultimate fate by the sequential differential activation of specific genes contained in each cell's genome. We have learned a great deal about how these genes functionally regulate each other in complex gene regulatory networks (GRN) in a handful of model species. This grant uses a powerful new model system to functionally understand how endodermal (gut) and mesodermal (e.g. muscle, blood, bone, kidney) arose from a common endomesodermal precursor. These novel data will provide insight into the significance of variations in the GRNs in different systems and suggest specific gene interactions involved in abnormalities in endomesodermal development.

描述（由申请人提供）：细胞在发育期间通过组合基因活性的差异途径获得其独特的命运。控制内中胚层细胞命运规范的基因调控网络（GRN）已经在一些模型系统中构建，包括海胆、脊椎动物和线虫。通过差异基因表达，产生内胚层（肠道衍生物）和中胚层（肌肉、血液、体腔、肾脏和骨骼元件）细胞类型的内中胚层前体细胞类型与外胚层前体细胞（产生表皮和神经系统）不同。随后从内中胚层前体中确定单独的内胚层和中胚层命运。了解细胞内因子和细胞外信号之间的关系，并重建不同动物物种之间的基因调控网络，可以为如何以及何时构建每种生物体的分子和形态特征提供关键见解。一个典型的例子是动物进化中中胚层胚层的原始进化外观。刺胞动物（海葵、珊瑚和“水母”）是一种动物群体，其成虫仅具有两个胚层、外胚层和双功能（具有吸收和收缩功能）胃胚层（肠道）层的衍生物。刺胞动物是其他拥有全部三个胚层的双侧对称动物的现存近亲，并且令人信服的分子、基因组、发育和进化证据表明，刺胞动物的腹皮层是所有其他三叶细胞双侧动物中内胚层和中胚层胚层的进化前身。因此，解开这种刺胞动物“内中胚层”基因调控网络，将为了解GRN子电路如何在各种后生动物中被采用、重新连接或增选以产生新颖的、修饰的或专门的内中胚层特征提供必要的见解。这笔资助将在功能上重建刺胞动物海葵 Nematostella vectensis 中内中胚层形成的基因调控网络（其基因组已由 J.G.I（能源部）测序），使用 QPCR、全基因组微阵列、功能技术，如药物治疗、合成 mRNA 错误表达、翻译和剪接阻断吗啉代 方法和顺式监管分析。此外，我们将把所有获得的数据应用到现有的基因表达数据库中，以便与科学界分享我们的发现。首次从系统发育关键物种中生成高质量的分子数据，将有助于通过极化进化变化的方向来解释先前在两侧对称模型系统中发现的基因差异及其调控相互作用。 公共健康相关性：项目叙述 发育中的动物胚胎中的单个细胞通过每个细胞基因组中包含的特定基因的连续差异激活来了解其最终命运。我们已经了解了大量关于这些基因如何在少数模型物种的复杂基因调控网络（GRN）中相互功能调节的知识。该资助使用一个强大的新模型系统来从功能上理解内胚层（肠道）和中胚层（例如肌肉、血液、骨骼、肾脏）如何从共同的内中胚层前体产生。这些新数据将深入了解不同系统中 GRN 变异的重要性，并提出与内中胚层发育异常有关的特定基因相互作用。