CONTROL OF AXIAL MUSCLE DEVELOPMENT

决定、分化和模式化的形态发生是核心 在发展过程中，但控制它们的机制还没有 令人满意的识别。 这些进程可供 分析在一个简单的脊椎动物系统中， 从鸡胚胎的上皮皮节中提取的。 试点研究 表明皮节在紧密的细胞周期下产生两种细胞表型， 空间控制。 此外，这种生成模式可以改变 实验性的 一个简单的手术就能使皮肤细胞形成群体 形成肌细胞。 此外，皮节引起轴向 在四肢和胸部水平表现出不同命运的肌肉。 为 例如，初步结果表明，皮节细胞程序性死亡 阻止了四肢水平的外侧轴肌的发育，并建议 这种死亡是由肢体组织的相互作用引起的。 建议的研究集中在细胞生成的空间控制， 系统和控制细胞生成模式的相互作用， 肌肉的命运 五个目标的研究将1）精细地描绘出 皮肤细胞和表征肌肉的发展， 皮节，2）评估空间限定的皮节的多能性 种群，3）定义控制模式化世代的相互作用 的肌细胞和真皮细胞，4）定义的相互作用，控制 中轴肌的节段特异性命运，以及5）评估 通过定义表达模式和使用 实验操作。 这些入路结合了联合收割机解剖学方法， 命运映射策略和胚胎手术 这项工作将有助于 阐明控制特定的模式化生成的机制， 细胞类型和肌肉的形态发生， 是人类正常发展的基础

Determination, differentiation, and patterned morphogenesis are central processes during development, but the mechanisms controlling them have yet to be satisfactorily identified. These processes are accessible to analysis in a simple vertebrate system, the development of axial muscle from the epithelial dermatome in the chicken embryo. Pilot studies suggest that the dermatome generates two cell phenotypes under a tight spatial control. Furthermore, this generation pattern can be altered experimentally. A simple surgery causes the dermacyte-forming population to form myocytes instead. Moreover, the dermatome gives rise to axial muscles that manifest different fates at limb and thoracic levels. For instance, preliminary results show that programmed death of dermatome prevents development of lateral axial muscles at limb levels and suggest that this death is induced by an interaction with limb tissue. Proposed studies focus on the spatial control of cell generation in this system and the interactions controlling cell generation patterns and muscle fate. Studies in five aims will 1) finely map the fate of dermatome cells and characterize the development of muscles derived from dermatome, 2) assess the pluripotency of spatially defined dermatomal populations, 3) define interactions that control the patterned generation of myocytes and dermacytes, 4) define interactions that control the segment-specific fates of axial muscles and 5) assess the relevance of putative regulatory genes by defining expression patterns and using experimental manipulations. The approaches combine anatomical methods, fate-mapping strategies and embryonic surgeries. This work will help elucidate mechanisms that control the patterned generation of specific cell types and the morphogenesis of muscles, processes that are fundamental to normal human development.