The molecular basis of planarian regeneration

涡虫再生的分子基础

• 批准号: 8469048
• 负责人: Alejandro Sanchez Alvarado
• 金额: $ 26.32万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469048
• 关键词: Address; Adult; Amputation; Animals; Biological; Biological Assay; Biological Models; Cell physiology; Cluster Analysis; Comparative Study; Complex; DNA; Developmental Gene; Double-Stranded RNA; Embryo; Event; Funding; Gene Expression; Genes; Genetic; Genetic Epistasis; Genome; Goals; Head; Health; Homeostasis; Human; Investigation; Mammals; Measures; Methods; Molecular; Molecular Profiling; Natural regeneration; Organ; Organ Specificity; Organogenesis; Pathway interactions; Pattern; Pharyngeal structure; Phyllanthus emblica; Planarians; Population; Process; RNA Interference; Resolution; Rest; Signal Pathway; Signal Transduction; Specificity; Stem cells; Testing; Therapeutic; Tissues; Totipotent Stem Cells; Vertebrates; Wound Healing; base; body system; density; developmental plasticity; frontier; functional genomics; gene function; genome sequencing; genome-wide; human stem cells; novel; regenerative; research study; response; tissue regeneration

Our objective is to identify and functionally characterize the genes and genetic pathways underpinning metazoan regeneration. We propose to use the planarian Schmidtea mediterranea as a model system to address this problem because it is among the simplest cephalized bilaterians with complex organ systems that display extensive regenerative capacities: a decapitated animal will regenerate and functionally integrate a new head to the pre-existing tissues in under a week. In addition, such remarkable developmental plasticity is driven by an abundant and experimentally accessible population of totipotent stem cells known as neoblasts. The advances made during the last period of funding to interrogate gene function and measure regenerative responses, combined with the sequencing and recent annotation of the S. mediterranea genome create an unprecedented opportunity to frame the problem of animal regeneration in molecular and functional genomic terms. We propose to take full advantage of the throughput capacity and biological plasticity afforded by planarians to establish a detailed molecular landscape of regeneration. We propose to: 1) carry out genome- wide, high temporal resolution analyses of regeneration using high density DNA arrays; 2) test the functions of key, evolutionarily conserved embryonic signaling pathways in the adult contexts of tissue homeostasis and regeneration to provide a functional basis for interpreting the microarray experiments; and 3) to carry out screens of organ-specific regeneration to determine the regulatory extent and degree of molecular specialization that exists in general regenerative events. Combined, these studies should provide us with the most comprehensive mechanistic study of regeneration performed to date, and should serve as a platform to formally test the evolutionary divergence or convergence of regeneration among animals, a central unresolved aspect hindering the implementation of rational regenerative therapeutics in poor regenerators such as mammals.

我们的目标是确定和功能特征的基因和遗传途径 支持后生动物的再生我们建议使用涡虫Schmidtea 作为解决这一问题的示范系统，因为它是 具有复杂器官系统的最简单的头状两侧动物， 再生能力：一个被斩首的动物将再生和功能整合， 一周内把新的头移植到原有的组织上此外，如此引人注目的 发育可塑性是由丰富的和实验上可获得的 一群全能干细胞称为新母细胞。2000年期间取得的进展 研究基因功能和测量再生反应的最后一段资金， 结合S.地中海基因组 创造了一个前所未有的机会， 分子和功能基因组术语。我们建议充分利用 通过能力和生物可塑性所提供的Planarians建立一个 详细的再生分子景观。我们建议：1）进行基因组- 使用高密度DNA阵列对再生进行宽范围、高时间分辨率的分析; 2)测试关键的，进化上保守的胚胎信号通路的功能， 成年人的组织稳态和再生的背景，以提供功能基础 用于解释微阵列实验;以及3）进行器官特异性的筛选， 再生以确定分子特化的调节范围和程度 存在于一般的再生事件中。综合起来，这些研究应该能为我们提供 迄今为止进行了最全面的再生机制研究， 应该作为一个平台，正式测试进化的分歧或趋同 再生的动物，一个核心的未解决的方面阻碍了 在较差的再生器中实施合理的再生治疗， 哺乳动物