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

基本信息

批准号：
8118980
负责人：
MARK q MARTINDALE
金额：
$ 25.94万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
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/8118980
关键词：
Adopted Adult Anemone Animals Appearance Architecture Binding Sites Bioinformatics Biological Biological Models Blood Cells Cellular Structures Cnidaria Communities Complex Connective Tissue Data Databases Development Developmental Gene Ectoderm Elements Embryo Endoderm Endomesoderm Epidermis Evolution Gene Components Gene Expression Generations Genes Genome Genomics Germ Layers Gland Goals Grant In Situ In Situ Hybridization Individual Invertebrates Jellyfish Kidney Learning Life Link Mesoderm Mesoderm Cell Messenger RNA Microinjections Modeling Molecular Muscle Nematoda Nervous system structure Oligonucleotides Organism Outcome Pathway interactions Pattern Pharmaceutical Preparations Pharmacologic Substance Phylogenetic Analysis Population RNA RNA Splicing Regulation Regulator Genes Regulatory Element Relative (related person)Research Resolution Sea Anemones Sea Urchins Signal Transduction Skin Specific qualifier value System Techniques Time Tissue-Specific Gene Expression Translations Variant Vertebrates Work base bone cell type combinatorial comparative comparative genomics coral extracellular fly functional genomics gene function gene interaction genome sequencing insight knock-down molecular phenotype novel public health relevance skeletal tool transcription factor

项目摘要

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）：细胞通过在发育时期组合基因活性的差异途径获得其独特的命运。控制内胚层细胞命运规范的基因调节网络（GRN）已在少数模型系统中构建，包括海胆，脊椎动物和线虫。产生内胚层（肠道衍生物）和中胚层（肌肉，血液，腔，肾脏，肾脏和骨骼元素）细胞类型的内胚层前体与外胚层前体（产生表皮和神经系统产生）不同的基因表达不同。然后，从内胚层前体中指定单独的内皮和中胚层命运。了解细胞内因子与细胞外信号之间的关系，以及重建不同动物物种之间的基因调节网络，可以为如何以及何时建立每个生物体的分子和形态特征提供关键见解。一个主要的例子是动物进化中中胚层生殖层的原始进化外观。 cnidarians（珊瑚，珊瑚和“水母”）是一个动物群体，其成年人只有两个衍生物，具有两个细菌层，外胚层和一个双功能（具有吸收性和收缩功能）gastodermal（gastodermal（肠））层。 Cnidarians是其他双侧对称动物的最亲密的亲戚，它们具有所有三个胚芽层，并且存在引人注目的分子，基因组，发育和进化证据，以证明胃胃皮是内胚层和中霉菌的所有其他三层动物的进化前体。因此，阐明这种cnidanian“内胚层”基因调节网络将提供必要的见解，以了解如何在各种内唑烷中采用，重新连接或选择GRN子电路，以引起新颖，改良或专业的内胚层胚层特征。 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方法和顺式调节性分析。公共卫生相关性：开发动物胚胎中的项目叙事单个细胞通过对每个细胞基因组中包含的特定基因的顺序差异激活来学习其最终命运。我们已经了解了有关这些基因在复杂基因调节网络（GRN）中如何在少数模型物种中相互调节的大量知识。该赠款使用强大的新模型系统在功能上了解内胚层（肠道）和中胚层（例如肌肉，血液，骨，骨，肾脏）是如何源自常见的内胚层前体的。这些新的数据将提供有关不同系统中GRN变化的重要性的洞察力，并提出与内胚膜发育异常有关的特定基因相互作用。