Evolutionary Origin of Vertebrate Neural Crest Gene Networks

脊椎动物神经嵴基因网络的进化起源

• 批准号: 7470012
• 负责人: Marianne Bronner
• 金额: $ 38.85万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470012
• 关键词: Address; Cells; Chick Embryo; Chickens; Chordata; Data; Dentin; Development; Ectoderm; Elements; Embryo; Event; Evolution; Family; Fibroblast Growth Factor; Fishes; Ganglia; Gene Expression; Genes; Genetic Epistasis; Goals; Head; Individual; Jaw; Lampreys; Link; Mediating; Modeling; Multipotent Stem Cells; Mus; Myxoid cyst; Neural Crest; Neural Crest Cell; Neural tube; Neurons; Nucleic Acid Regulatory Sequences; Oligonucleotides; Pathway interactions; Pattern; Peripheral; Petromyzon marinus; Phase; Phenotype; Population; Proteins; Regulator Genes; Reporter; Route; Sensory; Signal Transduction; Site; Snails; Specificity; Stem cells; Testing; Transcriptional Activation; Translations; Up-Regulation; Vertebrates; Xenopus; Zebrafish; base; bone; cell type; gene conservation; gene function; knock-down; loss of function; melanocyte; member; multipotent cell; neural plate; novel; promoter; relating to nervous system; research study; slug; transcription factor

DESCRIPTION (provided by applicant): Evolution of vertebrates has been intimately linked to the advent of the neural crest, a migratory and multipotent cell population that gives rise to many defining characters of vertebrates, including a well-defined head and peripheral ganglia. These multipotent progenitor cells form at the border of neural and non-neural ectoderm in vertebrate embryos. The regulatory interactions predicted to underlie neural crest formation involve inductive signals (e.g. Wnt, BMP, FGF) that establish the neural plate border, by up-regulation of border specifier genes like Msx1/2, Pax3/7, and Zic. These border genes in turn regulate neural crest specifier genes like Slug/Snail, FoxDS and the SoxE family. Finally, neural crest specifiers turn on specific downstream targets that render the neural crest migratory and multipotent. The goal of the proposed study is to address whether the neural crest gene regulatory network of traditional vertebrate models is conserved to the base of vertebrates. Data from non-vertebrate chordates suggest this network is a vertebrate novelty and that neural crest evolution involved cooption of several transcriptional regulators to the neural plate border of the vertebrate ancestor. We will compare the neural crest gene regulatory network of traditional vertebrate models with that of sea lamprey, jawless fish that represent the most primitive extant vertebrates. Our preliminary results suggest that many neural crest derivatives, early migratory routes and some components of the neural crest gene network are conserved in lamprey. We will test for conservation at the level of deployment of these molecules at the neural plate border as well as ability to carry out similar functions. To explore events that led to the evolution of this important cell type and thus to the origin of vertebrate features, this proposal will address the following specific aims: 1) Examine whether key genes that function as neural plate border and neural crest specifiers are conserved in sequence and distribution between jawless and jawed vertebrates. 2) Establish connections within the network by morpholino-mediated knock-down of selected transcription factors; establish epistasis by examining the consequences on expression of other genes in the network and their ability to rescue the loss-of-function phenotype. 3) Isolate regulatory regions of amphioxus and lamprey "specifier genes."

描述（由申请人提供）：脊椎动物的演变与神经rest的出现密切相关，神经rest的出现是一种迁移和多能细胞种群，引起了许多定义的脊椎动物特征，包括明确定义的头部和外围神经节。这些多能祖细胞在脊椎动物胚胎中神经和非神经外胚层的边界形成。通过神经rest形成的基础预测的调节相互作用涉及通过上调MSX1/2，PAX3/7和ZIC来建立神经板界的电感信号（例如Wnt，BMP，FGF）。这些边界基因反过来调节神经rest temifier基因，例如slug/蜗牛，狐狸和索斯家族。最后，神经rest指定器打开了使神经rest迁移和多能体系的特定下游目标。拟议的研究的目的是解决传统脊椎动物模型的神经克雷斯特基因调节网络是否保守了脊椎动物的基础。来自非脊椎动物弦的数据表明，该网络是一种脊椎动物的新颖性，神经冠的演变涉及将几个转录调节剂的库存到脊椎动物祖先的神经板界。我们将比较传统脊椎动物模型的神经rest基因调节网络与代表最原始的现存脊椎动物的lamp鼠，无知的鱼类的神经基因调节网络。我们的初步结果表明，许多神经rest衍生物，早期迁移途径和神经克雷斯特基因网络的某些组成部分在七lamp虫中保守。我们将在这些分子在神经板边界的部署水平上进行保护，以及执行相似功能的能力。为了探索导致这种重要细胞类型的演变以及脊椎动物特征的起源的事件，该提案将解决以下特定目的：1）检查起作用的关键基因作为神经板边框和神经冠状说明符是否在颌骨和颌骨之间保持序列和分布。 2）通过形态介导的选定转录因子的敲击在网络中建立连接；通过检查网络中其他基因表达的后果及其挽救功能丧失表型的能力来建立上毒。 3）两栖和七lamp虫的“指定基因”的分离区域。