GENE EXPRESSION IN THE DEVELOPING AND AGING HEART

在过去的几年里，心血管系统已经成为 最令人兴奋的研究分子机制的新领域 控制和维持器官形态。最近的融合 经典的胚胎学方法与品种的遗传分析 生物体的进化导致了多种遗传因子的发现 指导心脏祖细胞的规格， 时空控制其差异。新的遗传 心肌发生和形态发生之间的界面也已经被 揭示从最近的这些突破来看， 很明显，许多先天性疾病和问题，具体到 衰老的心脏只能通过追溯它们的起源来理解， 胚胎发育。此外，很明显，对于庞大的 经济投资在人类心血管研究，以支付， 深入了解心脏的遗传机制 发展和老龄化不仅是必要的，但一些问题， 紧迫 这个试点项目的目标是汇集我们两个人的专业知识， 实验室开发一个重要的资源，这将有助于 心脏器官发生的全面解剖。我们建议开设 一个包含10,000个DNA序列的目录，这些DNA序列代表了在人类基因组中表达的基因。 小鼠胚胎线形心管。该目录将被开发 作为心脏表达基因的交互式数据库， 可以识别序列，建立相互关系， 单个克隆迅速分离。曾经是新的或已知的基因， 感兴趣的人在屏幕上被识别，他们的表达模式将 在胚胎期成人和衰老的心脏组织中进行比较。数据库 将成为心脏领域的一种新的重要试剂。 它 可以广泛传播，并直接适用于迅速 扩大主动了解遗传电路的基础 心脏发育以及这种回路在适应不良的人中是如何失效的， 衰老的心脏

In the last few years the cardiovascular system has emerged as one of the most exciting new areas for studying the molecular mechanisms controlling and maintaining organ morphology. The recent fusion of classical embryological approaches with genetic analysis in a variety of organisms has resulted in the discovery of multiple genetic factors guiding the specification of cardiac progenitor cells and the spatiotemporal controls underlying their differentiation. New genetic interfaces between heart myogenesis and morphogenesis have also been revealed. From these recent breakthroughs, it is becoming increasingly clear that many of the congenital pathologies and problems specific to the aging heart can only be understood by tracing their origins in embryonic development. Moreover, it seems clear that for the huge economic investinent in human cardiovascular research to pay off, a thorough understanding of the genetic mechanisms acting in heart development and aging is not only necessary, but a matter of some urgency. The goal of this pilot project is to pool the expertise of our two laboratories to develop an important resource that will facilitate a comprehensive dissection of cardiac organogenesis. We propose to create a catalogue of 10,000 DNA sequences representing genes expressed in the murine embryonic linear heart tube. This catalogue will be developed as an interactive database of heart-expressed genes from which novel sequences can be identified, inter-relationships established, and individual clones rapidly isolated. Once novel or known genes of interest are identified in the screen, their expression patterns will be compared in embrvonic adult and aging heart tissue. The database will constitute a novel and imnortant reagent in the heart field. It can be broadly disseminated and is directly applicable to the rapidly expanding initiative to understand the genetic circuitry underlying heart development and how this circuitry fails in the maladapted, diseased and aging heart.