DEVELOPMENTAL ORIGIN OF THE MUSCLE SPINDLE

肌梭的发育起源

• 批准号: 2265701
• 负责人: JAN KUCERA
• 金额: $ 11.57万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265701
• 关键词: afferent nerve; biomarker; cell differentiation; colchicine; cytoskeletal proteins; denervation; efferent nerve; electron microscopy; embryo /fetus; gastrocnemius muscle; immunochemistry; innervation; laboratory rat; light microscopy; mechanoreceptors; motor neurons; muscle cells; myofibrils; myogenesis; myosins; nerve endings; neuroanatomy; neuronal transport; neurotrophic factors; striated muscles; afferent nerve; biomarker; cell differentiation; colchicine; cytoskeletal proteins; denervation; efferent nerve; electron microscopy; embryo /fetus; gastrocnemius muscle; immunochemistry; innervation; laboratory rat; light microscopy; mechanoreceptors; motor neurons; muscle cells; myofibrils; myogenesis; myosins; nerve endings; neuroanatomy; neuronal transport; neurotrophic factors; striated muscles

This proposal is an inquiry into the myogenic and neural (efferent and afferent) mechanisms whereby undifferentiated muscle cells are trans- formed into the three types of intrafusal fiber (bag1, bag2, chain) in muscle spindles of the rat. First, the role of myogenic factors in the differentiation of the three types of intrafusal fiber will be examined in medial gastrocnemius muscles reinnervated in the presence of exogenous nerve growth factor following nerve crush at one of three perinatal periods, whereby the types of muscle substrates available for spindle formation at sites of afferent-muscle cell contacts are altered. Second, the role of motor innervation in the assembly of spindles and differenti- ation of intrafusal fibers will be examined in neonatal muscles reinnervated by afferents only following nerve crush and distal spinal cord extirpation at birth. Third, the mechanisms of the morphogenetic effect of afferents will be addressed by surveying sensory nerve terminals in spindles for the expression of neuroactive substances, and by blocking axoplasmic transport in afferents supplying immature spindles in order to determine whether trophic substances emanating from sensory terminals regulate the differentiation of spindles. Light and electron microscopic neuroanatomical and immunochemical techniques are utilized. Particular attention is paid to the effects of experimental manipulations on the expression of myosin heavy chain isoforms which are markers of contractile proteins in intrafusal fibers. The developing spindle is a unique, naturally-occurring model for studying the interactions of three types of cell -- sensory neurons, motor neurons, and muscle cells -- in the course of formation and differentiation of a highly specialized class of muscle fibers. Investigation of afferent-muscle cell interactions addresses a poorly understood area of nerve-muscle interdependence during development. Research into the mechanisms of afferent-muscle interactions may provide evidence in favor of the existence of a sensory neurotrophic factor with a regulatory effect on myosin gene expression in muscle cells.

该提议是对肌原性和神经的调查（传出和 传入的）机制，从而无法分化的肌肉细胞是反式的 在三种类型的偶发性纤维（Bag1，Bag2，链条）中形成 大鼠的肌肉纺锤体。 首先，肌源性因素在 将检查三种类型的偶性纤维的区分 在内源性的情况下，在内侧肌肉肌肉中恢复了 在三个围产期之一的神经挤压后神经挤压后的神经生长因子 时期，可用于主轴的肌肉基板的类型 在传入肌肉细胞接触部位的部位形成。 第二， 运动神经在纺锤体和不同的组装中的作用 将在新生儿肌肉中检查恒星内纤维的attion 仅在神经挤压和脊柱远端的传入剂加剧 出生时绳索灭绝。 第三，形态发生的机制 传入的效果将通过调查感官神经来解决 纺锤体中的末端表达神经活性物质的表达和 通过阻止供应不成熟纺锤体的传入中的轴质传输 为了确定营养物质是否从感觉中散发出来 终端调节纺锤体的分化。 光和电子 使用微观神经解剖学和免疫化学技术。 特别注意实验操作的影响 关于肌球蛋白重链同工型的表达，这是 恒星纤维中的收缩蛋白。 开发主轴是一个独特的，自然的模型 研究三种类型的细胞 - 感觉神经元的相互作用， 运动神经元和肌肉细胞 - 在形成过程中 高度专业的肌肉纤维的区分。 对传入肌肉细胞相互作用的研究解决了不良的 在发育过程中了解了神经肌肉相互依存的区域。 研究传入肌肉相互作用的机制可能会提供 有利于存在感官神经营养因子的证据 对肌肉细胞中肌球蛋白基因表达的调节作用。