Mutational Analysis of Notochord Development

脊索发育的突变分析

• 批准号: 7928583
• 负责人: William Smith
• 金额: $ 4.92万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928583
• 关键词: Animals; Architecture; Area; Basement membrane; Biological Metamorphosis; Cell Polarity; Cells; Characteristics; Chordata; Complex; Defect; Development; Ectoderm; Embryo; Endoderm; Experimental Genetics; Frequencies; Funding; Genes; Genetic; Genome; Genomics; Gills; Grant; Human; Induced Mutation; Invertebrates; Knowledge; Laminin; Larva; Marines; Molecular; Morphogenesis; Mutagenesis; Mutation; Organ; Organism; Pathway interactions; Pattern; Phenotype; Population; Process; Proteins; Relative (related person); Research; Role; Screening procedure; Signal Pathway; Signal Transduction; Structure; System; Tissues; Vertebrates; ascidian; base; cell motility; interest; malformation; mutant; notochord; notochord development; positional cloning; relating to nervous system; research study; tool

DESCRIPTION (provided by applicant): An embryo goes from a single cell to a complex organism containing thousands of cells of multiple types. These cells assemble into tissues and organs with a precise architecture. The complexity of this architecture is at its most extreme in the group of animals that includes humans, the vertebrates. Research proposed here will use one of the closest invertebrate relatives of the vertebrates, the ascidian. Ascidians are primitive marine chordates that have the same basic architecture, or body plan, as the vertebrates, but as embryos have much fewer cells, and are under the control of a much smaller genome. Experiments proposed here will exploit developmental mutants to investigate two processes: the morphogenesis of the notochord and the patterning of the non-neural ectoderm. The notochord is one of the defining characteristics of the chordates, and the notochord is an important experimental paradigm for understanding tissue morphogenesis, specific experiments will focus on the role of a laminin gene product in organizing and directing the cells of the notochord to form a coherent tissue. In the absence of this gene product the notochord cells wander endlessly through the body. Experiments will explore how the laminin gene product interacts with previously characterized cell-signaling pathways known to be important in directing notochord cell motility. A second type of mutant that will be investigated disrupts the patterning of the trunk ectoderm of the ascidian larva. In this mutant various malformations are evident, the most interesting being the lack-of specific ectodermal thickenings that appear to be similar to vertebrate placodes. In the absence of these placode-like structures, the development of other tissues, in particular the pharyngeal endoderm, is abnormal. Specific aims are targeted at identifying the gene responsible for generating this phenotype, and understanding its normal function.

描述（由申请人提供）：胚胎从一个单细胞变成一个包含数千个多种类型细胞的复杂生物体。这些细胞组装成具有精确结构的组织和器官。这种结构的复杂性在包括人类在内的脊椎动物群体中表现得最为极端。这里提出的研究将使用脊椎动物最接近的无脊椎动物亲戚之一，海鞘。海鞘是一种原始的海洋脊索动物，具有与脊椎动物相同的基本结构或身体计划，但作为胚胎，它们的细胞要少得多，并且受更小的基因组控制。这里提出的实验将利用发育突变体来研究两个过程：脊索的形态发生和非神经外胚层的模式。脊索是脊索动物的定义特征之一，脊索是理解组织形态发生的重要实验范式，具体实验将侧重于层粘连蛋白基因产物在组织和指导脊索细胞形成连贯组织中的作用。在缺乏这种基因产物的情况下，脊索细胞在体内无休止地游荡。实验将探索层粘连蛋白基因产物如何与先前已知的在指导脊索细胞运动中重要的细胞信号通路相互作用。第二种将被研究的突变体破坏了海鞘幼虫躯干外胚层的图案。在这个突变体中，各种畸形是明显的，最有趣的是缺乏特定的外胚层增厚，这似乎与脊椎动物的基板相似。在缺乏这些基板样结构的情况下，其他组织的发育，特别是咽内胚层，是不正常的。具体目标是确定负责产生这种表型的基因，并了解其正常功能。