Developmental Co-dependence and Embryonic Programming of Cardiac and Renal Systems Function in Vertebrates - II

脊椎动物心脏和肾脏系统功能的发育相互依赖性和胚胎编程 - II

• 批准号: 1025823
• 负责人: Warren Burggren
• 金额: $ 80.63万
• 依托单位: University of North Texas
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1025823&HistoricalAwards=false
• 关键词: Developmental; Co; dependence; Embryonic; Programming

This project has three distinct but inter-related themes, each building on the next through an integrated physiological systems approach. Initially, the lab will explore, for the very first time, the embryonic interactions of two major systems - the cardiovascular system (CVS) and the renal system - and how their developmental plans are codependent upon each other as the vertebrate embryo develops. Also to be investigated is the developmental onset of the normal regulatory interactions between the CVS and renal system, including determination of developmental periods of greatest sensitivity to external stressors- the so-called "critical windows". Third, the enigmatic field of delayed phenotype alteration -so-called "fetal programming"- of the CVS and kidneys will be explored. The hypotheses will be tested by applying environmental and/or pharmaceutical stressors to the embryo and then assessing the physiological changes in the embryo and adult bird. The experiments will also begin to identify underlying cellular and molecular mechanisms that manifest in structural and functional modifications. This work transcends the typical "intrasystem" approach of most studies of structure/function relationships in developing vertebrates. Indeed, it represents one of the first experimental programs to look across - rather than just within - physiological systems in the developing vertebrate embryo. This study will greatly improve the understanding of the development of the embryonic CV and renal systems, and when and how these systems first begin their interactions, making important advances in the ontogeny of physiological regulation between, rather than just within, systems. An enhanced understanding of embryonic physiology in vertebrates - especially phenomena like developmental plasticity and particularly fetal programming - is a vital prerequisite for the eventual development of corrective procedures for congenital defects in human fetuses and even embryos. Graduate and undergraduate students will receive state-of-the-art training in the Developmental Physiology and Genetics program at the University of North Texas and interactions with researchers at the Universidad Autonoma del Estado de Mexico will provide them with important cultural and international perspectives.

该项目有三个不同但相互关联的主题，每个主题都通过综合生理系统方法建立在下一个主题之上。最初，该实验室将首次探索两个主要系统-心血管系统（CVS）和肾脏系统-的胚胎相互作用，以及它们的发育计划如何在脊椎动物胚胎发育时相互依赖。还需要研究的是CVS和肾脏系统之间的正常调节相互作用的发育起始，包括确定对外部应激源最敏感的发育期-所谓的“关键窗口”。第三，将探索CVS和肾脏的延迟表型改变的神秘领域-所谓的“胎儿编程”。 将通过对胚胎施加环境和/或药物应激源，然后评估胚胎和成年鸟的生理变化来测试这些假设。 这些实验也将开始以确定在结构和功能修饰中表现出的潜在细胞和分子机制。 这项工作超越了典型的“intrasystem”的方法，大多数研究的结构/功能的关系，在发展中的脊椎动物。事实上，它代表了第一个实验项目之一，以查看整个-而不仅仅是在-发育中的脊椎动物胚胎的生理系统。 这项研究将大大提高对胚胎CV和肾脏系统发育的理解，以及这些系统何时以及如何首次开始相互作用，在系统之间而不仅仅是系统内的生理调节的个体发育方面取得重要进展。加强对脊椎动物胚胎生理学的理解-特别是像发育可塑性和特别是胎儿编程这样的现象-是最终开发人类胎儿甚至胚胎先天性缺陷矫正程序的重要先决条件。研究生和本科生将在北德克萨斯大学的发育生理学和遗传学课程中接受最先进的培训，并与墨西哥自治大学的研究人员进行互动，为他们提供重要的文化和国际视野。