REGULATION OF CARDIAC MYOFIBRILLOGENESIS

描述：(改编自《调查者摘要》)开发过程中 收缩蛋白经历一种精确的关联，称为 肌原纤维形成。进一步的互动是必要的，以形成 对收缩能力至关重要的杆状表型。这些相互作用在 细胞骨架成分、膜受体(整合素)和细胞外基质 肌细胞杆状生长形成的基础。形成 细胞外基质-整合素复合体被认为是肿瘤传递的关键元件 机械信号传给心肌细胞。PI已经证明了构图和 细胞外基质的定位、整合素的存在和细胞骨架的排列 蛋白质对于杆状表型的形成是必不可少的。这些 进一步的研究表明，胶原基质上的肌细胞呈杆状。 细胞外基质-整合素复合体的表型和空间表达组分。 假设：完整的细胞外基质-整合素-细胞骨架连接对 心肌细胞的表型和功能。此外，ECM的布置和类型 通过整合素作用的成分可以调节心肌细胞的形状和组装 转化为一种能对化学和机械反应的表型 与体内观察到的信号相似。建议的研究包括：目标1- 确定细胞外基质、整合素和细胞骨架在肌原纤维形成和修复中的作用 体外表型。目标2-确定机械张力在 表型的形成和维持。目标3-确定这些因素如何 利用全胚胎调节原位心脏肌原纤维的形成和表型 文化。

DESCRIPTION: (Adapted from the Investigator's Abstract) During development contractile proteins undergo a precise association known as myofibrillogenesis. Further interactions are necessary to form the rod-shaped phenotype essential to contractility. These interactions between cytoskeletal components, membrane receptors (integrins) and ECM are fundamental for formation of rod-shaped growth of myocytes. Formation of ECM-integrin complex is proposed to be critical element in transmission of mechanical signals to myocyte. PI has shown that composition and orientation of ECM, presence of integrins, and alignment of cytoskeletal proteins are essential to the formation of rod-shaped phenotype. These studies further show that myocytes on collagen matrix assume rod-shaped phenotype and spatially express components of ECM-integrin complex. Hypothesis: an intact ECM-integrin-cytoskeletal linkage is critical to myocyte phenotype and function. Also, the arrangement and type of ECM components acting via integrins can regulate myocyte shape and the assembly of myofibrils into a phenotype that can respond to chemical and mechanical signaling similar to that observed in vivo. Proposed studies are: Aim 1 - Determine role of ECM, integrins, and cytoskeleton on myofibrillogenesis and phenotype in vitro. Aim 2 - Determine role of mechanical tension in formation and maintenance of phenotype. Aim 3 - Determine how these factors regulate myofibrillogenesis and phenotype in situ heart using whole embryo culture.