Pre-patterning of Skeletal Muscle

骨骼肌的预成型

• 批准号: 6317844
• 负责人: Steven Burden
• 金额: $ 33万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6317844
• 关键词: agrin; axon; biological signal transduction; cell differentiation; cholinergic receptors; electrophysiology; gene expression; gene targeting; genetically modified animals; immunocytochemistry; in situ hybridization; innervation; laboratory mouse; muscle proteins; myoblasts; myofibrils; neuromuscular junction; protein structure function; striated muscles; synaptogenesis; tissue /cell culture

DESCRIPTION (From the Applicant's Abstract): Current ideas of synapse formation suggest that muscle is patterned by signals, such as agrin, provided by motor neurons. Our recent studies, however, have revealed that muscle is pre-patterned in the absence of innervation. We found that motor axons in top 2b mutant embryos reach their targets but fail to grow or branch within limb or diaphragm muscles. To our surprise, we found that AChRs are clustered in the central region of muscle, despite the absence of motor axons within the muscle. These results suggest that the expression pattern of AChRs in skeletal muscles is determined, at least in part, by mechanisms that are autonomous to muscle and suggest that muscle is pre-patterned, independent from signals provided by motor neurons. The experiments described in this proposal are designed to determine how pre-patterning of muscle is established, whether muscle pre-patterning might regulate where axons terminate and form synapses and how innervation might regulate muscle pre-patterning. We will determine (1) whether motor innervation requires neural or muscle expression of top 2b, (2) whether signals from motor axons are required to pre-pattern AChRs in skeletal muscle, (3) whether MuSK or agrin are required to establish muscle pre-patterning, (4) whether additional skeletal muscle proteins are pre-patterned in muscle, (5) whether genes encoding synaptic proteins are pre-patterned in muscle, (6) whether pre-patterned molecules might have a role in specifying the site of motor innervation, (7) whether motor axons or electrical activity suppress muscle pre-patterning, and (8) whether a distinct myoblast lineage might be a source of the pre-pattern.

描述（摘自申请人的摘要）：当前的突触形成思想 暗示肌肉是由电动机提供的信号（例如Agrin）图案的 神经元。然而，我们最近的研究表明肌肉是 在没有神经上的情况下预先展示。我们发现顶部的运动轴突 2B突变胚达到目标，但无法在肢体内生长或分支 隔膜肌肉。令我们惊讶的是，我们发现Achrs聚集在 肌肉的中心区域，尽管肌肉内没有运动轴突。 这些结果表明骨骼肌中ACHR的表达模式 至少部分通过自主的肌肉机制来确定 并建议肌肉是预制的，独立于提供的信号 运动神经元。本提案中描述的实验旨在 确定如何建立肌肉的预性 预制可能会调节轴突终止和形成突触的位置以及如何 神经可能调节肌肉的预生使。我们将确定（1）是否 运动神经支配需要前2B的神经或肌肉表达，（2）是否 需要从运动轴突中的信号才能在骨骼肌肉中预先pattern ACHR， （3）是否需要麝香或阿格林来建立肌肉预制，（4） 其他骨骼肌蛋白是否在肌肉中预先展示，（5） 编码突触蛋白的基因是否在肌肉中预先模仿，（6） 预先图案的分子是否可能在指定位置 运动神经支配，（7）运动轴突还是电活动抑制 肌肉预制，（8）明显的成肌谱系是否可能是 预制的来源。