The molecular basis of planarian regeneration

我们的目标是识别和确定基因和遗传途径的功能特征 支撑后生动物的再生。我们建议使用蓝藻施密特茶 地中海作为解决这一问题的模式系统，因为它是 最简单的头化双侧动物，具有复杂的器官系统，表现出广泛的 再生能力：被斩首的动物将再生，并在功能上整合 在不到一周的时间里将新的头部移植到预先存在的组织中。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 全能干细胞群被称为新生成骨细胞。在此期间所取得的进展 最后一期的资金用于询问基因功能和测量再生反应， 结合稻瘟病菌基因组的测序和最新注释 创造一个前所未有的机会来框定动物再生问题 分子和功能基因组学术语。我们建议充分利用 行星生物提供的吞吐能力和生物可塑性 详细的再生分子图景。我们建议：1)进行基因组- 使用高密度DNA阵列进行广泛、高时间分辨率的再生分析； 2)测试关键的、进化上保守的胚胎信号通路在 为成人背景下的组织动态平衡和再生提供了功能基础 用于解释微阵列实验；以及3)进行器官特异性筛选 再生以确定分子特化的调节程度和程度 普遍存在于再生事件中。总而言之，这些研究应该会为我们提供 进行了迄今为止最全面的再生机制研究，以及 应该作为正式测试进化分歧或趋同的平台 动物之间的再生，一个中心悬而未决的方面阻碍了 合理的再生疗法在不良再生器中的实施 哺乳动物。

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.