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的相互作用 类型。肢体的主要组成部分之一是骨骼肌。这个 “蓝图”或指定精确排列和区分的计划 骨骼肌的纤维类型是在发育早期形成的 与肢体和大脑的神经支配密切相关 结缔组织的组织化影响。在这里提出的研究 重点关注这些相互作用在建立和 维持肌纤维类型的早期模式，控制 在此背景下肌肉纤维的后续发展 “蓝图”。这些问题将在两个正在制定的 鸡和大鼠的后肢使用胚胎操作的组合，在 体外培养程序和免疫化学分析。在活体内， 纤维类型和发育阶段特定亚型的表达将是 分析了在四肢当中正常相互作用的连接词 组织和肌肉以及神经和肌肉已被改变或破坏。在……里面 骨骼肌细胞的培养、发育和自我特化能力 A)完全不与其他类型的细胞相互作用，以及b)在 与运动神经元和肌肉“成纤维细胞”共培养将被检测。 初步数据表明，这种相互作用可能通过以下方式影响表达 做出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 肌细胞类型的表达及其重建 文化中的互动将是一个重要的概念和 理解细胞调控机制的方法学进展 发育过程中的基因表达和肌纤维多样化。

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.