Notch-Gridlock Signaling in Vascular Specification

血管规范中的Notch-Gridlock信号传导

• 批准号: 6838222
• 负责人: TAO P ZHONG
• 金额: $ 30.2万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-23 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6838222
• 关键词: alternatives to animals in research; angiogenesis; biofeedback; biological signal transduction; cell cell interaction; cell differentiation; cell migration; confocal scanning microscopy; developmental genetics; gene expression; gene mutation; genetic promoter element; genetic regulation; genetically modified animals; green fluorescent proteins; high throughput technology; in situ hybridization; protein quantitation /detection; protein signal sequence; time resolved data; transcription factor; vascular endothelium; zebrafish

DESCRIPTION (provided by applicant): Vascular development requires a complex series of events during which endothelial cells differentiate from angioblast progenitors and assemble into the dorsal aorta and the cardinal vein, comprising the original circulatory loop. Arteries and veins are morphologically, functionally and molecularly different. How this distinction is established at cellular and molecular levels in the early stage of vasculogenesis is largely unknown. New genetic evidence from zebra fish studies suggests that the Notch signal transduction pathway is required for vascular specification. The gridlock gene, encoding an Enhancer of Split-related bHLH protein, mediates Notch signaling to promote development of the embryonic arteries. The research proposal explains how cellular and genetic analysis are used in zebra fish to understand the role of notch-gridlock pathway in regulating arterial/venous endothelial fate of angioblasts. Specially, this proposal first aims to identify potential cell-cell interactions by following angioblast migration. Next, experiments are designed to examine expression pattern of Notch signaling components in vascular development, as well as to determine the fate of individual angioblasts that are incapable of normal Notch signaling. The final experiments are proposed to test the mechanism by which gridlock mediates Notch signaling via a negative feedback loop. As fundamentals of vascular development are conserved between vertebrates and mammals, understanding the notch-gridlock signaling pathway in zebrafish will provide insights into mechanisms of vascular development as well as advance our understanding of etiologies of many human arterial diseases.

描述（由申请人提供）：血管发育需要一系列复杂的过程，在此过程中，内皮细胞从成血管细胞祖细胞分化并组装成背主动脉和主静脉，构成原始的循环回路。动脉和静脉在形态、功能和分子上都是不同的。在血管发生的早期阶段，这种区别是如何在细胞和分子水平上建立起来的，这在很大程度上是未知的。