MYOFIBRIL AND MYOFIBER FORMATION IN THE DEVELOPING HEART

产品说明： （根据申请人摘要修改）正常发育 需要细胞外基质和细胞外基质之间的相互作用 和单个细胞成分。 各种复杂的相互作用 导致细胞表型和模式所必需的有效 心脏功能不同类型的肌细胞的形成似乎 与肌原纤维发生相关。 这种协调 涉及ECM、特异性跨膜 受体和细胞骨架。 虽然很多人都知道， 组装的肌原纤维，很少有人知道的作用， 排列肌节或附着肌原纤维的细胞骨架 到细胞膜和细胞器。 拟议的研究将：1）审查 ECM受体（整合素）、细胞骨架成分和细胞核 核纤层蛋白在体外肌原纤维发生中作用; 2）使用特异性抗体， 反义寡核苷酸探针和生长因子干扰 肌原纤维的形成; 3）比较在 体外至全胚胎培养模型中的肌原纤维发生;以及4） 确定肌原纤维发生的改变是否会导致肌纤维模式的改变 在整个胚胎培养中形成肌细胞。 小鼠胎心细胞 将用于一种独特的培养系统， 表型与体内观察到的相似。 初步调查将 检查黏着斑蛋白、α-辅肌动蛋白和整合素在 肌原纤维形成显微注射反义寡核苷酸和/或 抗体将用于阻断与肌原纤维的相互作用， 发展的关键时期。 类似的探头将用于整个 胚胎培养以确定异常的肌细胞生成是否会 导致异常的纤维模式。这些数据将共同提供 加强对肌原纤维组装及其关系的认识 心脏器官形成的关键

DESCRIPTION: (Modified from applicant's abstract) Normal development of the heart requires an interaction between the extracellular matrix and individual cellular components. A complex variety of interactions result in the cellular phenotypes and patterns necessary for efficient cardiac function. Formation of distinct patterns of myocytes appears to be coordinately associated with myofibrillogenesis. This coordination involves an interaction between the ECM, specific transmembrane receptors and the cytoskeleton. While much is known considering the assembly of myofibrils, little is known concerning the role of the cytoskeleton in alignment of sarcomeres or the attachment of myofibrils to membranes and organelles. The proposed studies will: 1) examine the role of ECM receptors (integrins), cytoskeletal components and nuclear lamins in myofibrillogenesis in vitro; 2) use specific antibody, antisense oligonucleotide probes and growth factors to perturb the formation of myofibrils; 3) compare the patterns and alterations seen in vitro to myofibrillogenesis in the whole embryo culture model; and 4) determine if altered myofibrillogenesis causes altered myofiber pattern formation of myocytes in whole embryo culture. Mouse fetal heart cells will be used in a unique culture system that produces myocytes with a phenotype similar to that seen in vivo. Initial investigations will examine the expression of vinculin, alpha-actinin, and integrins during myofibrillogenesis. Microinjection of antisense oligonucleotides and/or antibodies will be used to block inter- actions with myofibrils at critical times in development. Similar probes will be used in whole embryo culture to determine whether abnormal myofibrillo- genesis will result in abnormal fiber patterns.Together, these data will provide an enhanced understanding of myofibrillar assembly and its relation- ship to cardiac organogenesis.