NEGATIVE FACTOR WHICH REGULATES CARDIAC DEVELOPMENT

对心肌发生和心肌细胞增殖的认识 分化必须涉及多个复杂的基因控制系统 发展中的监管。细胞骨架蛋白、波形蛋白和 Desmin，提供了一个很好的模型系统来破译基因是如何 在心脏分化过程中“关闭”或激活。波形图 合成首先在中胚层的描绘处被检测到。一个数字 的细胞类型从这个谱系中分化出来，并继续合成 而其他人则喜欢心脏“关闭”波形蛋白基因和 激活肌肉特异基因结蛋白。这项提议的目标是 确定波形蛋白基因失活所需的条件。 显然，这一早期发展决策中的任何缺陷都可能导致 基因表达异常，影响心脏发育。 以前的研究表明有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。负性蛋白质 因子在胚胎发育过程中积累，这至少在 部分原因是关闭了波形蛋白基因。这种沉默蛋白出现了 在雏鸡心脏发育的早期，在卵子的第18天增加了14倍。 这一增加与波形蛋白mRNA的下降大致平行，后者是 在六天大的鸡身上几乎检测不到。一种类似的蛋白质是 发现于小鼠、大鼠和人类细胞中，因此，它似乎普遍存在于 大多数模型开发系统。因为消音器蛋白相当于 丰富的心灵，我们怀疑它对监管其他 除了波形蛋白外，还有其他基因。事实上，它还可以用来协调 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。这项提议的目标是 为了表征这些顺式作用序列和涉及到的蛋白质因子 心脏发育过程中波形蛋白基因的调控。由于它的新颖性 特别强调的是消音器蛋白。在这里，积极的 参与波形蛋白基因调控的因素及可能的其他基因 受这一规定的约束。最终，我们会隔离消音器 蛋白质，它的基因和基因。了解消音器基因是如何 受监管，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 In fact, it may also serve to coordinate cell growth and gene not clear whether or not myocytes are reversibly withdrawn from cell-cycle during development.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.