The roles of FoxH1 and TGFbeta signaling in directing asymmetric cardiac morphogenesis

FoxH1 和 TGFbeta 信号传导在指导不对称心脏形态发生中的作用

• 批准号: 1147123
• 负责人: Rebecca Burdine
• 金额: $ 45.08万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1147123&HistoricalAwards=false
• 关键词: roles; FoxH1; TGFbeta; signaling; directing

How cells are arranged in three dimensions to produce functional organs such as the heart is a fundamental question in biology that has not been fully addressed. Once cells are instructed to become heart tissue, they must coordinate their movements to organize into a multi-layered functional structure. One critical aspect of this process is how cells arrange differently on the left versus the right side of the heart, commonly referred to as left-right patterning. Previous work has determined that the FoxH1 transcription factor plays an important role in integrating multiple TGFbeta signals in heart cells so that they respond appropriately to left-right patterning information. Utilizing the powerful genetics available in the zebrafish system, the roles of FoxH1 in coordinating TGFbeta signaling and directing left-right cell migrations in the developing heart will be explored. The outcome of this work will be a better understanding of how the heart forms, especially with regards to left-right patterning. This information will have significant impact on stem cell studies aimed at producing functional organs for transplant. This project is well suited to be conducted by graduate students and undergraduates and will be the framework for recruiting women and underrepresented minorities into research through thesis work at Princeton and through the Summer Research Experience program conducted by the Department of Molecular Biology.

细胞如何在三维空间中排列以产生功能器官，如心脏，这是生物学中的一个基本问题，尚未得到充分解决。一旦细胞被指示成为心脏组织，它们必须协调它们的运动来组织成一个多层的功能结构。这个过程的一个关键方面是细胞在心脏左侧和右侧的排列方式不同，通常被称为左右模式。先前的工作已经确定FoxH1转录因子在整合心脏细胞中的多个tgf β信号中起重要作用，从而使它们对左右模式信息做出适当的反应。利用斑马鱼系统中强大的遗传学，FoxH1在协调TGFbeta信号传导和指导心脏发育中左右细胞迁移中的作用将被探索。这项工作的结果将是更好地理解心脏是如何形成的，特别是关于左-右模式。这一信息将对旨在产生用于移植的功能性器官的干细胞研究产生重大影响。这个项目非常适合研究生和本科生进行，并将成为通过普林斯顿大学的论文工作和分子生物系开展的暑期研究体验项目招募女性和代表性不足的少数民族进行研究的框架。