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: 7491370
• 负责人: Marianne Bronner
• 金额: $ 65.81万
• 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/7491370
• 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

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."

脊椎动物的进化与神经嵴的出现密切相关，神经嵴是一种迁徙和 多能细胞群，产生脊椎动物的许多定义特征，包括定义明确的 头部和周围神经节。这些多能祖细胞形成于神经和非神经的交界处， 脊椎动物胚胎的外胚层。预测为神经嵴形成基础的调节相互作用 涉及诱导信号（例如Wnt、BMP、FGF），其通过上调 边界指定基因如Msx 1/2、Pax 3/7和Zic。这些边缘基因反过来调节神经嵴 如Slug/Snail、FoxDS和SoxE家族的特异性基因。最后，神经嵴指定符打开特定的 下游的目标，使神经嵴迁移和多能性。拟议研究的目标是 为了解决传统脊椎动物模型的神经嵴基因调控网络是否保守， 脊椎动物的基础来自非脊椎动物脊索动物的数据表明，这种网络是脊椎动物的新奇事物 神经嵴的进化涉及到几种转录调节因子对神经板的共同选择 脊椎动物祖先的边界。我们将比较传统的神经嵴基因调控网络 脊椎动物模型与海七鳃鳗，无颌鱼，代表最原始的现存脊椎动物。 我们的初步结果表明，许多神经嵴衍生物，早期迁移路线和一些 神经嵴基因网络的组成部分在七鳃鳗中是保守的。我们将在 这些分子在神经板边缘的部署水平以及进行类似的神经传导的能力。 功能协调发展的为了探索导致这一重要细胞类型进化的事件， 根据脊椎动物的特征，该提案将针对以下具体目标： 1)检查作为神经板边界和神经嵴指定符的关键基因是否保守 无颚脊椎动物和有颚脊椎动物之间的序列和分布。 2)通过吗啉代介导的选择性转录的敲低在网络内建立连接 因素;建立上位性通过检查的结果对其他基因的表达， 网络和它们拯救功能丧失表型的能力。 3)分离文昌鱼和七鳃鳗特异性基因调控区。"