Cellular and Molecular Mechanisms of Myotube Pathfinding
肌管寻路的细胞和分子机制
基本信息
- 批准号:10240575
- 负责人:
- 金额:$ 32.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsActomyosinAllelesAreaBehaviorBiochemicalBiological AssayBiologyCellsChemotaxisCollectionCuesDataDefectDevelopmentDiseaseDrosophila genusEmbryoFibroblast Growth FactorFibroblast Growth Factor ReceptorsFilopodiaGene Expression ProfilingGenesGeneticGenetic ScreeningHumanImageKnowledgeMolecularMorphogenesisMuscleMuscle DevelopmentMuscle FibersMuscle hypotoniaMutationMyoblastsMyopathyNamesNotch and Wnt Signaling PathwayOutcomePathway interactionsPatientsPhosphotransferasesProtein KinaseProtein-Serine-Threonine KinasesPublishingRegulatory PathwayRoleSarcomeresSignal TransductionSiteSite-Directed MutagenesisSkeletal MuscleTechniquesTendon structureTestingTransgenic OrganismsTropomyosinWaspsWorkclinical phenotypecongenital myopathyearly onsetextracellulargenetic regulatory proteinin vivoinsightmutantmyogenesisnovelprotein functionpublic health relevancereceptorrespiratorytool
项目摘要
Project Summary
Congenital myopathies (CM) are a heterogeneous collection of disorders defined by early onset
hypotonia. Some myopathies can progress to extreme conditions in which patients develop
respiratory complications and even require assistance for mobility. Mutations in genes associated
with actin dynamics have been identified in patients with CMs, including Tropomyosins. We found
that Drosophila Tropomyosin 2 (Tm2) directs embryonic skeletal muscle development by promoting
myoblast fusion, myotube elongation, and sarcomere assembly. These surprising results argue that
defects in myofiber development contribute to the clinical phenotypes associated with CMs.
There remain critical knowledge gaps in our understanding of skeletal muscle development. In
particular, nascent myotubes must elongate and attach to the appropriate tendon cells to form a
functional contractile unit. However, the molecules that guide myotubes to their muscle attachment
sites remain largely unknown. In addition, the mechanisms by which myotubes respond to
chemotactic signals are unclear. We have used forward genetic screens and cutting edge
transcriptional profiling to identify myotube guidance molecules and intracellular effectors of myotube
elongation. Our preliminary work has generated unique genetic tools and novel mechanistic insights
that will allow us to characterize the central pathways and mechanisms that direct myotube
elongation. The overall hypothesis for this application is that filopodia are the key effectors of
myotube pathfinding, and that filopodial behavior is dictated by external pathfinding cues, intracellular
protein kinases, and actin regulatory proteins. This project will achieve the following aims: (1) define
the cellular pathways by which Tropomyosin regulates myogenesis, (2) characterize novel
intracellular effectors of myotube pathfinding, and (3) characterize chemotactic mechanisms that
direct myotube pathfinding. These studies will make substantial inroads into an emerging area of
muscle biology that has the potential to uncover novel mechanisms that contribute to muscle disease.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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AARON N JOHNSON其他文献
AARON N JOHNSON的其他文献
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{{ truncateString('AARON N JOHNSON', 18)}}的其他基金
Multi-organism platform for functional assessment of human birth defect associated genomic variants
用于人类出生缺陷相关基因组变异功能评估的多生物体平台
- 批准号:
10568668 - 财政年份:2022
- 资助金额:
$ 32.54万 - 项目类别:
Cellular and Molecular Mechanisms of Myotube Pathfinding
肌管寻路的细胞和分子机制
- 批准号:
9260424 - 财政年份:2016
- 资助金额:
$ 32.54万 - 项目类别:
Cellular and Molecular Mechanisms of Myotube Pathfinding
肌管寻路的细胞和分子机制
- 批准号:
9770532 - 财政年份:2016
- 资助金额:
$ 32.54万 - 项目类别:
Cellular and Molecular Mechanisms of Myotube Guidance
肌管引导的细胞和分子机制
- 批准号:
10659818 - 财政年份:2016
- 资助金额:
$ 32.54万 - 项目类别:
Role of the novel protein family CAMSAP in heart, muscle and tracheal development
新型蛋白质家族 CAMSAP 在心脏、肌肉和气管发育中的作用
- 批准号:
7624648 - 财政年份:2008
- 资助金额:
$ 32.54万 - 项目类别:
Role of the novel protein family CAMSAP in heart, muscle and tracheal development
新型蛋白质家族 CAMSAP 在心脏、肌肉和气管发育中的作用
- 批准号:
7405851 - 财政年份:2008
- 资助金额:
$ 32.54万 - 项目类别:
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