Interaction Affecting Craniofacial Muscle Differentiatio

描述（由申请人提供）：颅面肌肉显示出巨大的结构 和功能的多样性，以及他们发展中的异常， 视力、面部表情、咀嚼和 发声然而，人们对控制这些过程的过程知之甚少。 鳃肌和眼外肌的分化和成熟。头 肌肉出现在邻近大脑的间充质中，然后迁移， 分化为源自神经嵴的结缔组织。躯干和 肢肌起源于上皮肌节，然后分化为近轴肌节， 侧中胚层这项研究将描述必要的组织相互作用 (1)促进鳃肌和眼外肌的早期分化 （2）直接表达纤维类型特异性肌球蛋白， 这些肌肉中的肌管。这些相互作用将通过 移植特定的肌肉前体，在不同的阶段，并与或 没有假定的肌肉诱导组织，在头部和躯干轴向水平之间。 组织反应的测定包括成肌细胞标志物（例如，天哪， 约，myoD），躯干或头部肌肉特异性标志物（例如，parc aboutcis， pax 3; pod 1，barx 2，Ibx 1，en 2），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鸡胚上进行的， 适用于体内组织重组实验， 头部肌肉的细胞和分子生物学是唯一可用的。一 第三个具体的目标将描述颅面 肌肉在以后的生长和成熟阶段改变它们的附着。EM 研究表明，初级肌管在其生长期发生局灶性变性， 在胚胎第12-15天，在肌腱尖端和肌管中部区域。 我认为，这些局灶性变性是必不可少的正常重塑， 头部肌肉，但没有什么是已知的过程或挑衅，这些 焦点损失对已知在治疗期间有活性的途径的元素的测定 单核细胞的程序性细胞死亡将应用于正常和 功能或生长停滞的头部肌肉。总的来说，这些实验 提供对启动所需信号的初步了解， 颅面肌的不同分化及其机制 这些头部肌肉的重塑发生。

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.