REGULATION OF CARDIAC MYOFIBRILLOGENESIS

描述：（改编自研究者摘要）开发期间 收缩蛋白质经历一种精确的关联， 肌原纤维形成 进一步的相互作用是必要的， 对收缩性至关重要的杆状表型。 这些互动之间 细胞骨架成分、膜受体（整合素）和ECM是 是形成肌细胞棒状生长的基础。 形成 ECM-整合素复合物被认为是在传播的关键因素， 机械信号传递给肌细胞。 PI表明，组合物和 ECM的方向、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需的。 这些 研究进一步表明胶原基质上的肌细胞呈杆状 ECM-整合素复合物的表型和空间表达组分。 假设：完整的ECM-整联蛋白-细胞骨架连接对于 肌细胞表型和功能。 此外，ECM的布置和类型 通过整联蛋白起作用的组分可以调节肌细胞的形状和组装 转化为一种表型， 类似于在体内观察到的信号传导。 拟议的研究是：目标1 - 确定ECM、整合素和细胞骨架在肌原纤维发生和 体外表型。 目的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 利用全胚胎在体心脏调控肌原纤维发生和表型 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.