CELL INTERACTIONS AND THE DEVELOPMENT OF SKELETAL MUSCLE

脊椎动物肢体的正常发育依赖于 在各种细胞和组织之间建立适当相互作用 类型 肢体的主要组成部分之一是骨骼肌。 的 “蓝图”或计划，明确安排和区分 骨骼肌的纤维类型在发育的早期就已确定 并与肢体的神经支配和 结缔组织的组织影响。 这里提出的研究 关注这些相互作用在建立和 维持肌纤维类型的早期模式， 在这种情况下，肌肉纤维的后续发展 “蓝图”。 这些问题将在发展中国家和 鸡和大鼠后肢使用胚胎操作的组合， 体外培养程序和免疫化学分析。 在体内 纤维类型和发育阶段特异性同种型的表达将是 在肢体中进行分析，其中连接物之间的正常相互作用 组织、肌肉、神经和肌肉都被改变或破坏。 在 培养，肌肉细胞的发育和自我特化能力， a）完全不存在与其他细胞类型的相互作用，和B）在 将检查与运动神经元和肌肉“成纤维细胞”的共培养。 初步数据表明，这种相互作用可能会影响表达， 在文化中通常不明显的明显差异。 识别调节和控制细胞间的相互作用， 肌细胞类型的表达和这些细胞类型的重建 文化的相互作用既是一个重要的概念， 在理解细胞机制方面的方法学进展 基因表达和肌纤维多样化在发展过程中。

The normal development of the vertebrate limb is dependent on the establishment of appropriate interactions among various cell and tissue types. One of the major components of the limb is skeletal muscle. The "blueprint" or plan specifying the precise arrangement and differentiation of the fiber types of skeletal muscle is established early in development and in close temporal association with innervation of the limb and the organizing influence of the connective tissue. The studies proposed here focus on the role of that these interactions play in establishing and maintaining the early pattern of muscle fiber types and controlling the subsequent development of the muscle fibers within the context of this "blueprint". These questions will be addressed in both the developing chicken and rat hindlimbs using a combination of embryo manipulations, in vitro culture procedures, and immunochemical analyses. In vivo, the expression of fiber type- and developmental stage-specific isoforms will be analyzed in limbs in which the normal interactions between the connective tissue and muscle and nerve and muscle has been altered or disrupted. In culture, the development and self-specializing capacity of muscle cells in a) the complete absence of interaction with other cell types, and b) in coculture with motorneurons and muscle "fibroblasts" will be examined. Preliminary data suggest that such interactions may affect expression by making explicit differences which are not normally apparent in culture. The identification of cell interactions that regulate and control the expression of muscle cell types and the reconstruction of these interactions in culture would be both an important conceptual and methodological advance in understanding the cellular mechanisms controlling gene expression and muscle fiber diversification during development.