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DEVELOPMENT OF MOTONEURONAL CONNECTIVITY

运动神经连接的发展

基本信息

批准号：
2416266
负责人：
Monte Westerfield
金额：
$ 26.91万
依托单位：
UNIVERSITY OF OREGON
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-07-01 至 1998-12-31
项目状态：
已结题

项目摘要

Inductive interactions between cells regulate many aspects of vertebrate development, including formation and patterning of the nervous system. Failures of inductive signaling give rise to a wide variety of birth and developmental defects. Despite the obvious importance and many types of inductive interactions required for vertebrate development, the cellular and molecular mechanisms that regulate such interactions are, for the most part, poorly understood. This proposal seeks a more detailed understanding of a developmental signaling process that induces formation of the first muscle cells, termed muscle pioneers. Analysis of zebrafish embryos has shown that muscle pioneers arise and take on their specialized cell-fates, distinct from other muscle cells, as a result of inductive influences from the notochord. To learn when and where these interactions between the notochord and muscle occur, notochord precursors cells, will be a) removed by laser ablation at various times during the inductive process, b) followed with fluorescent dyes in live developing embryos, and c) grown in culture in the presence of muscle precursors. To understand the genetic regulation of the induction process, interactions between two mutations, ntl and spt, that perturb formation of muscle pioneers, will be characterized. The induction of muscle pioneers will be assayed after transplanting a) wild-type notochord precursor cells into ntl mutants, which lack notochords, b) notochord precursors from spt mutants, which lack muscle pioneers, into ntl mutants, and c) wild-type precursors into ntl/spt double mutants. By determining the conditions for rescue of notochord, muscle pioneers, and both, the precise cellular requirements for the induction and the functions of the genes identified by these mutations will be learned. To begin identifying the molecular genetic mechanisms underlying the inductive process, genes expressed in muscle pioneers in response to notochord induction will be characterized by analyzing their promoters and their functions in transgenic fish, and new mutations that affect the formation of muscle pioneers and muscle patterning will be recovered and characterized.

细胞之间的诱导相互作用调节脊椎动物的许多方面发育，包括神经系统的形成和模式。感应信号的失败会导致各种各样的出生和出生发育缺陷。尽管其重要性显而易见且种类繁多脊椎动物发育所需的诱导相互作用，细胞对于大多数人来说，调节这种相互作用的分子机制是部分，理解甚少。该提案旨在更详细地了解发展诱导第一个肌肉细胞形成的信号传导过程，称为肌肉先锋。对斑马鱼胚胎的分析表明，肌肉先驱者的出现并承担了他们特殊的细胞命运，与其他肌肉细胞，由于感应影响脊索。了解脊索和脊索之间相互作用的时间和地点肌肉发生时，脊索前体细胞，将被 a) 通过激光去除在感应过程中的不同时间消融，b) 随后活体发育胚胎中的荧光染料，以及 c) 在培养物中生长肌肉前体的存在。为了了解诱导过程的遗传调控，两种突变（ntl 和 spt）之间的相互作用，扰乱了肌肉先锋，将被表征。肌肉先锋的诱导将在移植后进行测定 a) 野生型脊索前体细胞转化为缺乏脊索的 ntl 突变体，b) 来自 spt 的脊索前体将缺乏肌肉先锋的突变体转化为 ntl 突变体，以及 c) 野生型 ntl/spt 双突变体的前体。通过确定条件拯救脊索、肌肉先锋以及两者，精确的细胞诱导要求和已识别基因的功能通过这些突变将被学习。开始识别潜在的分子遗传机制诱导过程，肌肉先锋中表达的基因响应脊索诱导将通过分析其启动子和它们在转基因鱼中的功能，以及影响肌肉先锋的形成和肌肉模式将得到恢复特点。