Proximo-Distal Patterning in the Drosophila Appendages

果蝇附肢的近远端模式

• 批准号: 8037945
• 负责人: RICHARD S MANN
• 金额: $ 34.22万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8037945
• 关键词: Address; Animals; Biological Models; Cells; Chromatin Structure; Complex; Cues; Defect; Development; Disease; Dissection; Distal; Dorsal; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; Enhancers; Epidermal Growth Factor; Fingers; Funding; Gene Expression; Gene Targeting; Genes; Genetic Enhancer Element; Goals; Hour; Intrinsic factor; Label; Left; Leg; Malignant Neoplasms; Medicine; Molecular; Mutation; Pathway interactions; Pattern; Play; Positioning Attribute; Primordium; Process; Regulatory Element; Research; Role; Signal Transduction; Stem cells; To specify; Wing; Work; appendage; cell fate specification; cell type; embryonic stem cell; extracellular; fascinate; insight; research study; transcription factor

DESCRIPTION (provided by applicant): Animal development depends on the successive refinement of cell fates and cell potentials. Embryonic stem cells, for example, are pluripotent but their descendents gradually take on more specific fates depending on the extracellular cues they perceive and intrinsic factors they express. Understanding this process at a mechanistic level is important for eventually harnessing the potential of stem cells for medicine, as well as for understanding many diseases, such as cancers, where this process fails to be properly regulated. In this project, the model system to be investigated is appendage specification in the fruit fly, Drosophila melanogaster. One goal is to understand, at a molecular level, how the initial leg and wing primordia become established in the early embryo. A second goal is to characterize the mechanism by which cis-regulatory enhancer elements integrate signaling and transcription factor inputs during the formation of the proximal- distal axis in the leg. A third goal is to investigate how the Epidermal Growth Factor pathway establishes positional information in the distal-most segments of the leg. Together, these Aims will provide significant insights into how appendages are first specified to how final positional information in the leg is achieved. PUBLIC HEALTH RELEVANCE: This project addresses fundamental processes during animal development, in particular, how cells gradually restrict their potentials as development proceeds. Stem cells, for example, are pluripotent, but some of their descendents have more limited potentials. When this process is not properly regulated, developmental defects and cancers can result.

描述（由申请方提供）：动物发育取决于细胞命运和细胞潜能的连续细化。例如，胚胎干细胞是多能的，但它们的后代会根据它们感知到的细胞外信号和表达的内在因子逐渐呈现出更特定的命运。在机械水平上理解这一过程对于最终利用干细胞的医学潜力以及理解许多疾病（如癌症）都很重要，在这些疾病中，这一过程未能得到适当的调节。在本计画中，研究的模式系统是果蝇的附肢特化。一个目标是在分子水平上了解最初的腿和翅膀原基是如何在早期胚胎中建立起来的。第二个目标是表征顺式调节增强子元件在腿中近端-远端轴形成期间整合信号传导和转录因子输入的机制。第三个目标是研究表皮生长因子途径如何在腿的最远段建立位置信息。总之，这些目标将提供重要的见解，如何附件首先指定的腿中的最终位置信息是如何实现的。 公共卫生关系：该项目涉及动物发育过程中的基本过程，特别是细胞如何随着发育的进行逐渐限制其潜力。例如，干细胞是多能的，但它们的一些后代具有更有限的潜力。当这一过程没有得到适当的调节时，可能会导致发育缺陷和癌症。