Interaction Affecting Craniofacial Muscle Differentiatio

描述(申请人提供)：头面部肌肉显示出很大的结构性 和功能多样性，以及它们发展过程中的反常现象，有助于 视力、面部表情、咀嚼等方面的广泛问题 发声。然而，人们对控制 颧肌和眼外肌的分化和成熟。头 肌肉在邻近大脑的间质中出现，然后迁移和 在源自神经脊的结缔组织中分化。中继线和 四肢肌肉起源于上皮性肌瘤，然后在近轴和近轴分化 侧中胚层。这项研究将描述必要的组织相互作用 (一)促进颧肌和眼外肌的早期分化 成肌细胞和(2)直接表达纤维类型特异性肌球蛋白。 这些肌肉中的肌管。这些交互作用将通过以下方式确定 移植特定的肌肉前体，在不同的阶段和与或 在头部和躯干的轴向水平之间，没有假定的肌肉诱导组织。 组织反应的分析包括成肌细胞标志物(例如，My， 关于，MyoD)，躯干或头部肌肉特异性标记(例如，Parc关于coutcis， Pax3；Pod1，Barx2，Ibx1，en2)，以及在肌肉特异性肌球蛋白的后期阶段 沉重的锁链。手术是在鹌鹑和小鸡的胚胎上进行的，这是理想的 适用于体内组织重组实验，并详细介绍了 头部肌肉的细胞和分子传记是独一无二的。一个 第三个特定的目标将描述颅面部的过程 肌肉在生长和成熟的后期改变它们的附着物。埃姆 研究表明，初级肌管在其 胚胎12-15天，肌腱顶端和肌管中段。 我认为这些局灶性退行性变对于正常的心脏重塑是必不可少的。 头部肌肉，但对这些肌肉的过程或刺激一无所知 局灶性损失。对已知在以下过程中活跃的通路元件的分析 单核细胞程序性死亡将应用于正常和 功能或生长受阻的头部肌肉。总而言之，这些实验将 提供对启动和启动所需信号的初步见解 颅面肌的不同分化及其机制 这些头部肌肉发生重塑。

DESCRIPTION (provided by applicant): Craniofacial muscles show great structural and functional diversity, and anomalies in their development contribute to a wide range of problems in vision, facial expression, mastication, and phonation. However, little is known about processes controlling the differentiation and maturation of branchial and extra-ocular muscles. Head muscles arise in mesenchyme adjacent to the brain then migrate and differentiate in connective tissues derived from the neural crest. Trunk and limb muscles arise in epithelial myotomes, then differentiate in paraxial and lateral mesoderm. This research will characterize tissue interactions necessary (1) to promote early differentiation of branchial and extra-ocular muscle myoblasts and (2) to direct expression of fiber typespecific myosins in primary myotubes in these muscles. These interactions will be identified by transplanting specific muscle precursors, at different stages and with or without putative muscle-inducing tissues, between head and trunk axial levels. Assays of tissue response include expression of myoblast markers (e.g., my, about, myoD), of trunk or head muscle-specific markers (e.g., parc aboutcis, pax3; podl, barx2, Ibxl,en2), and at later stages of muscle-specific myosin heavy chains. Surgeries are done on quail and chick embryos, which are ideally suited for in vivo tissue recombination experiments and for which detailed cellular and molecular biographies of head muscles are uniquely available. A third specific aim will characterize the processes by which craniofacial muscles change their attachments during later growth and maturation stages. EM studies reveal that primary myotubes undergo focal degeneration at their myotendinous tips and also at mid-myotube regions during embryonic days 12-15. I propose that these focal degenerations are essential for normal remodeling of head muscles, but nothing is known of the processes or provocations for these focal losses. Assays for elements of the pathways known to be active during programmed cell death of mononucleated cells will be applied to normal and function- or growth-arrested head muscles. Collectively, these experiments will provide the first insights into the signals necessary for initiation and diverse differentiations of craniofacial muscles and the mechanisms by which remodeling of these head muscles occurs.