Heart Morphogenesis in the Ascidian, Ciona Intestinalis

迈克尔·S·莱文，IOS-0745322肠囊类动物的心脏形态发生在人体等生物体中，体内的内脏均匀地分布在整个体腔中。然而，各个器官的“雏形”来自胎儿内部附近的位置。器官的有序排列依赖于“定向细胞迁移”，即特定器官(如心脏)的前体从起始点移动到成年身体的最终位置的过程。细胞定向迁移的中断会导致许多人类疾病，包括先天性心脏病(先天性心裂)。在脊椎动物胚胎中研究定向细胞迁移一直是非常困难的，即使是相对简单的脊椎动物，如鱼和青蛙，因为心脏和其他内脏的祖细胞在迁移时由数百或数千个细胞组成。在过去的几年里，莱文实验室已经开发出一种用于研究心脏迁移的简单模式生物--海鞘或海鞘，即海鞘。最近的各种分子研究表明，海鞘是与脊椎动物最接近的近亲，细胞迁移的基本机制可能同样用于海鞘和脊椎动物的心脏细胞迁移。然而，在海鞘蝌蚪中研究这一过程要容易得多，因为它由相对较少的细胞组成。在其迁徙时，海鞘心脏雏形只由四个细胞组成。在这项拟议的工作中，莱文实验室将识别和表征心脏细胞迁移所需的基因。这项研究揭示的基本机制应该适用于包括人类在内的脊椎动物的心脏细胞迁移。这项工作的更广泛影响包括使用一个强大而简单的模型系统来阐述心脏发育的基本原则，为Ciona社区生成资源，以及培训从本科生到博士后研究员的广泛研究人员。

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.