Mutational Analysis of Notochord Development

脊索发育的突变分析

基本信息

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
项目类别：
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

项目摘要

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）：胚胎从单个细胞转变为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最为复杂。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。海鞘是原始的海洋脊索动物，与脊椎动物具有相同的基本结构或身体结构，但胚胎的细胞要少得多，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。脊索是脊索动物的决定性特征之一，脊索是了解组织形态发生的重要实验范式，具体实验将重点关注层粘连蛋白基因产物在组织和指导脊索细胞形成连贯结构中的作用。组织。如果没有这种基因产物，脊索细胞就会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表征的细胞信号传导途径相互作用，这些信号传导途径已知对指导脊索细胞运动很重要。将要研究的第二种突变体破坏了海鞘幼虫躯干外胚层的模式。在这种突变体中，各种畸形是显而易见的，最有趣的是缺乏似乎与脊椎动物基板相似的特定外胚层增厚。在缺乏这些基板样结构的情况下，其他组织，特别是咽内胚层的发育是异常的。具体目标是识别负责产生这种表型的基因，并了解其正常功能。