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Developmental patterning of the anterior neural plate in a simple chordate

简单脊索动物前神经板的发育模式

基本信息

批准号：
8534308
负责人：
Michael Steven Levine
金额：
$ 31.6万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8534308
关键词：
Adult Anterior Biological Assay Biological Models Brain Caenorhabditis elegans Cell Lineage Cell Separation Cells Cephalic Chordata Ciona intestinalis Computer Simulation Development Developmental Process Dorsal Drosophila genus Ectopic Expression Electroporation Embryo Event Face Gene Combinations Gene Targeting Genes Genome Goals Head Heart Individual Invertebrates Label Larva Life Mesenchyme Methods Modeling Molecular Morphogenesis Neural Crest Neural tube Oceans Pattern Phylogenetic Analysis Pigments Pituitary Gland Process Regulator Genes Relative (related person)Research Resolution Sea Signal Pathway Signal Transduction Sister Spinal Cord Stomodeum Tadpoles Techniques Tissues Transgenic Organisms Urochordata Vertebrates Water ascidian cephalochordate cranium genetic analysis innovation migration neural plate notochord novel otoconia theories

项目摘要

DESCRIPTION (provided by applicant): We propose to use the sea squirt, Ciona intestinalis, as a simple chordate model to study key vertebrate developmental processes. Ciona embryos and larvae resemble simplified vertebrate tadpoles with a prominent notochord, dorsal hollow neural tube, and centralized brain. Recent molecular phylogenetic studies indicate that Tunicates (Urochordates) such as Ciona are the closest living relatives of the vertebrates. Ciona possesses a number of exceptional features for elucidating vertebrate developmental processes. The genome is small (~16,000 genes and 160 Mb) and lacks the whole-genome duplication events that bedevil functional genetic analyses in vertebrates. The tadpole is composed of only ~2,000 cells that arise from simple and well-defined lineages, comparable to those seen in C. elegans. It is possible to transform thousands of synchronously developing embryos with desired transgenic DNAs via electroporation. Simply put, the gene networks underlying key vertebrate developmental processes, such as specification of neural crest, are highly conserved in Ciona but not in C. elegans, Drosophila or other invertebrate model systems. The Gans and Northcutt "new head" theory proposed that most tissues of the vertebrate head represent novel innovations with no homologous counterparts in invertebrates. In vertebrates, these tissues arise from cranial neural crest and placodes, derived from the boundary between the neural tube and anterior neural plate. The focus of this revised proposal is the specification of the Ciona rudimentary cranial placodes and neural crest at the anterior border of the neural tube. We will use a combination of cell- specific labeling methods, cis-regulatory analysis, targeted misexpression assays, gene disruption methods, cell sorting techniques and computational modeling to delineate gene regulatory networks controlling these processes. The research plan includes the following three specific aims: (1) to determine gene regulatory networks governing the specification and invagination of the stomodeum and associated placodes; (2) to determine the gene networks regulating the specification of the putative pituitary; and (3) to characterize the specification of the pigmented otolith and ocellus, and identify Twist target genes responsible for the directed migration of mesenchyme and "synthetic" ectomesenchyme.

描述（由申请人提供）：我们建议使用海鞘（Ciona ninteinalis）作为简单的脊索动物模型来研究脊椎动物的关键发育过程。小蝌蚪的胚胎和幼虫类似于简单的脊椎动物蝌蚪，具有突出的脊索、背部中空的神经管和集中的大脑。最近的分子系统发育研究表明，被囊动物（尾脊索动物）如狮尾鱼是脊椎动物的近亲。在阐明脊椎动物的发育过程中，乔娜具有许多特殊的特征。基因组很小（约16000个基因和160mb），并且缺乏困扰脊椎动物功能遗传分析的全基因组复制事件。蝌蚪只由大约2000个细胞组成，这些细胞来自简单而明确的谱系，与秀丽隐杆线虫的谱系相当。通过电穿孔可以将数千个同步发育的胚胎转化为所需的转基因dna。简而言之，脊椎动物关键发育过程的基因网络，如神经嵴的规范，在Ciona中是高度保守的，而在秀丽隐杆线虫、果蝇或其他无脊椎动物模型系统中则不是。Gans和Northcutt的“新头”理论提出，脊椎动物头部的大多数组织代表了新的创新，在无脊椎动物中没有同源的对应体。在脊椎动物中，这些组织来自于颅神经嵴和基板，起源于神经管和前神经板之间的边界。这一修订方案的重点是在神经管的前边界的中脑区基本颅基板和神经嵴的规格。我们将结合细胞特异性标记方法、顺式调控分析、靶向错误表达测定、基因破坏方法、细胞分选技术和计算模型来描述控制这些过程的基因调控网络。该研究计划包括以下三个具体目标：(1)确定控制气孔和相关基板的规范和内陷的基因调控网络；(2)确定调节推定垂体规格的基因网络；(3)表征色素耳石和细胞的规格；