DEVELOPMENTAL SIGNALING OF SMOOTH MUSCLE DIFFERENTIATION

我们目前关于平滑肌细胞分化的知识 在胚胎发育的早期，严重缺乏。 很少有研究 涉及分子遗传学的最新进展， 这个关键的发展问题。 这一长期目标 建议是确定必要的发展信号， 平滑肌细胞的分化和成熟。 这些过程 在早期胚胎发育过程中需要精确的时间， 与各种组织的正常发育和功能有关 和器官。 研究表明，肌动蛋白的积累， 平滑肌细胞的分化是与血管生成相关的主要因素之一。 随着平滑肌细胞形态的发育成熟。 我们 初步研究表明，γ-肠肌动蛋白是关键， 在发育中的平滑肌细胞内发现的细胞骨架成分 胃肠道 在本申请中，我们提出检查 一种分子标记物诱导发育中大鼠肠道平滑肌细胞分化 γ-肠平滑肌肌动蛋白基因及其表达的分析。 我们将阐明γ-肠肌动蛋白的组织特异性表达 发育中大鼠胃肠道的mRNA及其分离、测序和鉴定 表征γ-肠肌动蛋白基因。 此外，我们将确定 假定的顺式作用调节结构域和反式作用调节结构域 与γ-肠平滑肌细胞正常表达相关的蛋白质 平滑肌肌动蛋白基因在平滑肌细胞分化过程中的作用。 我们 将利用这些研究作为基础，研究神经营养 交感神经节对神经细胞分化和成熟的影响 平滑肌细胞在发育中的大鼠胃肠道。 这些 研究将提供线索，以发展的信号， 发育期大鼠平滑肌细胞的分化 胃肠道 这些研究将提供线索， 与平滑肌分化相关的发育信号 发育中的老鼠肠道细胞。 这些过程的识别， 发育中的老鼠肠道将为我们理解 平滑肌细胞的分化和发育。 在 目前，我们对遗传或表观遗传调控的理解 任何重要的发育基因都缺乏。 建议的研究 这个应用程序将为我们提供独特的机会，开始， 解开这些复杂的问题与分化， 平滑肌细胞

Our current knowledge regarding the differentiation of smooth muscle cells during early embryonic development is severely lacking. Few studies involving the recent advances in molecular genetics have been directed at this critical developmental question. The long term objectives of this proposal are to determine the developmental signals necessary for the differentiation and maturation of smooth muscle cells. These processes require precise timing during early embryonic development and are intimatel associated with the normal development and function of a variety of tissues and organs. Studies have shown that the accumulation of actin within the differentiating smooth muscle cell is one of the primary factors associated with the development of the mature smooth muscle cell morphology. Our preliminary studies have demonstrated that gamma-enteric actin is the key cytoskeletal element found within the smooth muscle cells of the developing gastrointestinal tract. In this present application, we propose to examine smooth muscle cell differentiation in the developing rat gut by a molecular analysis of the gamma-enteric smooth muscle actin gene and its expression. We will clarify the tissue-specific expression of the gamma-enteric actin mRNA in the developing rat gastrointestinal tract and isolate, sequence and characterize the gamma-enteric actin gene. In addition, we will identify the putative cis-acting regulatory domains and trans-acting regulatory proteins associated with the normal expression of the gamma-enteric smooth muscle actin gene during the differentiation of smooth muscle cells. We will utilize these studies as a basis to investigate the neurotrophic influences of sympathetic ganglia on the differentiation and maturation of smooth muscle cells in the developing rat gastrointestinal tract. These studies will provide clues as to the developmental signals associated with the differentiation of smooth muscle cells in the developing rat gastrointestinal tract. These studies will provide clues as to the developmental signals associated with the differentiation of smooth muscle cells in the developing rat gut. The identification of these processes in the developing rat gut will provide the framework for our understanding of the differentiation and development of smooth muscle cells in general. At present, our current understanding of the genetic or epigenetic regulation of any developmentally important gene is lacking. The studies proposed in this application will provide us with the unique opportunity to begin to unravel these complex issues in association with the differentiation of smooth muscle cells.