NEGATIVE FACTOR WHICH REGULATES CARDIAC DEVELOPMENT

了解心肌发生和心肌细胞增殖， 分化必须涉及多个复杂的系统， 发展过程中的监管。 细胞骨架蛋白，波形蛋白和 结蛋白，提供了一个很好的模型系统，用于破译基因是如何 在心脏分化期间被“关闭”或激活。 波形蛋白 首先在中胚层的轮廓处检测到合成。 一些 的细胞类型从这一谱系分化，并继续合成 波形蛋白，而其他人喜欢心脏“关闭”波形蛋白基因， 激活肌肉特异性基因结蛋白 本提案的目的是 确定波形蛋白基因失活所需的条件。 显然，这种早期发育决策中的任何缺陷都可能导致 基因表达异常并损害心脏发育。 以前的研究表明，多个积极因素和至少一个消极因素 是肌肉组织中波形蛋白表达所必需的。 阴性蛋白 因子在胚胎发生过程中积累，这至少在 关闭波形蛋白基因的部分。 这种沉默蛋白 在鸡心脏发育的早期，到卵内第18天增加14倍。 这种增加与波形蛋白mRNA的下降大致平行， 在六日龄的鸡中几乎检测不到。 一种类似的蛋白质是 在小鼠，大鼠和人类细胞中发现，因此，它似乎是普遍的， 大多数发展模式。 因为沉默蛋白 在心脏中丰富，我们怀疑它对调节其他 基因除了波形蛋白。 事实上，它也可能有助于协调 细胞生长和基因尚不清楚肌细胞是否可逆 在发育过程中退出细胞周期。 这项提案的目的是 为了表征这些顺式作用序列和蛋白质因子， 心脏发育过程中波形蛋白基因的调控。 由于其新奇 将特别强调沉默蛋白。 给你，正能量 参与波形蛋白基因调控的因素以及其他可能的基因 受此规定约束。 最终，我们会分离出消音器 蛋白质、其cDNA和基因。 了解沉默基因是如何 在决定如何做出发展决策方面至关重要 在心脏胚胎发育的早期

An understanding of myogenesis and cardiac cell proliferation and differentiation must involve multiple, complex systems for controlling gene regulation during development. The cytoskeletal proteins, vimentin and desmin, provide an excellent model system for deciphering how genes are "turned-off" or activated during cardiac differentiation. Vimentin synthesis is first detected at the delineation of the mesoderm. A number of cell-types differentiate from this lineage and continue to synthesize vimentin, whereas others like heart "turn-off" the vimentin gene and activate the muscle-specific gene, desmin. The goal of this proposal is to determine what is required for the inactivation of the vimentin gene. Obviously, any defect in this early developmental decision could result in aberrant gene expression and compromise cardiac development. Previous work suggests multiple positive and at least one negative factor is required for vimentin expression in muscle tissue. The negative protein factor accumulates during embryogenesis which is responsible at least in part for turning-off the vimentin gene. This silencer protein appears early in chick heart development and increases 14-fold by day 18 in ovo. this increase roughly parallels the decline in vimentin mRNA which is barely detectable in chickens by six days of age. A comparable protein is found in mouse, rat and human cells and, therefore, it appears universal to most model developmental systems. Because the silencer protein is fairly abundant in heart, we suspect it is important for the regulation of other genes in addition to vimentin. In fact, it may also serve to coordinate cell growth and gene not clear whether or not myocytes are reversibly withdrawn from cell-cycle during development. The goal of this proposal is to characterize these cis-acting sequences and protein factors involved in vimentin gene regulation during cardiac development. Due to its novelty particular emphasis will be placed on the silencer protein. Here, positive factors involved in vimentin gene regulation and what other genes might be subjected to this regulation. Ultimately, we will isolate the silencer protein, its cDNA and gene. An understanding of how the silencer gene is regulated, is vital in determining how developmental decisions are made early in cardiac embryogenesis.