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

• 批准号: 8845622
• 负责人: Michael Steven Levine
• 金额: $ 32.83万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845622
• 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

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 Enteris）作为简单的脊索动物模型来研究关键的脊椎动物发育过程。海鞘胚胎和幼虫类似于简化的脊椎动物蝌蚪，具有突出的脊索、背侧中空神经管和中央大脑。最近的分子系统发育研究表明，诸如海鞘之类的被囊动物（尾索动物）是脊椎动物现存的最近亲。 Ciona 拥有许多阐明脊椎动物发育过程的特殊特征。基因组很小（约 16,000 个基因和 160 Mb），并且缺乏困扰脊椎动物功能遗传分析的全基因组重复事件。蝌蚪仅由约 2,000 个细胞组成，这些细胞源自简单且明确的谱系，与秀丽隐杆线虫中的细胞相当。通过电穿孔可以用所需的转基因 DNA 转化数千个同步发育的胚胎。简而言之，关键脊椎动物发育过程（例如神经嵴的规范）背后的基因网络在玻璃海鞘中高度保守，但在秀丽隐杆线虫、果蝇或其他无脊椎动物模型系统中则不然。甘斯和诺斯卡特的“新头部”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物。在脊椎动物中，这些组织源自颅神经嵴和基板，源自神经管和前神经板之间的边界。该修订提案的重点是神经管前缘的 Ciona 基本颅板和神经嵴的规范。我们将结合使用细胞特异性标记方法、顺式调控分析、靶向错误表达分析、基因破坏方法、细胞分选技术和计算模型来描绘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）确定控制口和相关基板规范和内陷的基因调控网络； (2) 确定调节假定垂体规格的基因网络； (3) 表征有色耳石和眼孔的规格， 并确定负责间质和“合成”外间充质定向迁移的 Twist 靶基因。