Heart Morphogenesis in the Ascidian, Ciona Intestinalis

海鞘、肠海鞘的心脏形态发生

• 批准号: 0745322
• 负责人: Michael Levine
• 金额: $ 50万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0745322&HistoricalAwards=false
• 关键词: Heart; Morphogenesis; Ascidian; Ciona; Intestinalis

Michael S. Levine, IOS-0745322Heart Morphogenesis in the Ascidian, Ciona intestinalisIn organisms such as humans, internal organs within the body are evenly distributed throughout the body cavities. However, the "rudiments" of the respective organs arise from nearby locations within the fetus. The orderly arrangement of the organs depends on "directed cell migration," a process whereby the precursors of a specific organ, such as the heart, move from its site of origin to its final location in the adult body. Disruptions in directed cell migration cause many human diseases, including congenital heart defects (cardia bifida). It has been very difficult to study directed cell migration in vertebrate embryos, even relatively simple vertebrates such as fish and frogs, since the progenitors of the heart and other internal organs consist of hundreds or thousands of cells at the time of their migration. During the past few years the Levine lab has developed a simple model organism for studying heart migration, the sea squirt or ascidian, Ciona intestinalis. A variety of recent molecular studies suggest that the sea squirts are the closest living relative of the vertebrates and the same basic mechanisms of cell migration are likely used for heart cell migration in sea squirts and vertebrates. However, it is much easier to study this process in the sea squirt tadpole since it is composed of relatively few cells. At the time of its migration the sea squirt heart rudiment is composed of just four cells. In the proposed work, the Levine lab will identify and characterize the genes required for heart cell migration. The basic mechanisms revealed in this study should apply to heart cell migration in vertebrates, including humans. The Broader Impacts of this work include the elaboration of the fundamental principles of heart development using a powerful, yet simple, model system, generation of resources for the Ciona community, and training of a wide range of researchers, from undergraduates to postdoctoral fellows.

Michael S. Levine，ios-0745322在海沿岸，ciona肠肠中有机体（例如人类）体内内部器官均匀分布在整个体腔中。但是，各个器官的“基础”来自胎儿内附近的位置。 器官的有序排列取决于“定向细胞迁移”，这一过程从特定器官（例如心脏）的前体从其原产地移动到其在成年体内的最终位置。定向细胞迁移的破坏会导致许多人类疾病，包括先天性心脏缺陷（Cardia bifida）。 很难研究脊椎动物胚胎中的定向细胞迁移，甚至相对简单的脊椎动物，例如鱼类和青蛙，因为心脏的祖细胞和其他内部器官在迁移时由数百或数千个细胞组成。在过去的几年中，Levine Lab开发了一种简单的模型生物体，用于研究心脏迁移，海洋喷水或海外ciona intestinalis。 最近的各种分子研究表明，海洋喷水是脊椎动物最接近的生物亲戚，并且可能使用相同的细胞迁移基本机制，用于海洋喷水和脊椎动物中的心脏细胞迁移。 但是，在海洋喷t t中研究此过程要容易得多，因为它由相对较少的细胞组成。 在迁移时，Sea Squirt Heart Rudiment仅由四个细胞组成。在拟议的工作中，Levine Lab将识别并表征心脏细胞迁移所需的基因。这项研究中揭示的基本机制应适用于包括人类在内的脊椎动物中的心脏细胞迁移。 这项工作的更广泛的影响包括使用强大而简单的模型系统，为Ciona社区的资源生成心脏发展的基本原理以及从本科生到博士后研究员的广泛研究人员的培训。