CONTROL OF AXIAL MUSCLE DEVELOPMENT

决定、分化和图案化的形态发生是核心 过程，但控制它们的机制还没有 令人满意地被识别。可以访问这些进程 在一个简单的脊椎动物系统中分析轴肌的发育 从鸡胚的上皮肤处提取的。试点研究 建议皮肤刀在紧致的压力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 试验性的。一个简单的手术就会导致皮肤细胞形成 形成肌细胞。此外，皮肤孔还会产生轴向 在四肢和胸部水平上表现出不同命运的肌肉。为 实例，初步结果显示皮肤病患者的程序性死亡 防止四肢水平的侧中轴肌发育，并建议 这种死亡是由与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上。 系统和控制细胞生成模式和 肌肉的命运。对五个目标的研究将精准地描绘出 皮肤部细胞，并表征肌肉的发育 皮肤刀，2)评估空间定义的皮肤瘤的多能性 种群，3)定义控制图案化世代的交互作用 肌细胞和真皮细胞，4)定义控制 轴肌的节段性命运和5)评估 通过定义表达模式和使用 实验性的操控。这些入路结合了解剖学方法， 命运地图战略和胚胎手术。这项工作将有所帮助 阐明控制特定图案生成的机制 细胞类型和肌肉的形态发生，这些过程 对人类的正常发展至关重要。

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.