Evolution of regeneration: a comparative study in annelids

再生进化：环节动物的比较研究

• 批准号: 0520389
• 负责人: Alexandra Bely
• 金额: $ 39万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0520389&HistoricalAwards=false
• 关键词: Evolution; regeneration; comparative; study; annelids

Animals vary dramatically in their ability to replace lost body parts through regeneration. The proposed work aims to answer two main questions by investigating closely related species with different regeneration abilities: (1) Which developmental processes fail in non-regenerating species? (2) Do the same developmental processes fail in different lineages that have independently lost regeneration abilities? The specific objectives of this proposal are to identify closely related regenerating and non-regenerating species, characterize developmental steps of normal early regeneration, and determine which of these steps fail to be initiated in species that have recently lost the ability to regenerate. Comparative regeneration experiments will be performed on a group of annelid (segmented) worms, the naidines, to investigate the phylogenetic distribution of regeneration ability. While many naidines have extensive abilities to regenerate parts of their anterior/posterior body axis, several species have been identified that have lost the capacity for anterior regeneration. More detailed developmental characterizations will be performed on three anteriorly regenerating species and two independently derived nonanteriorly regenerating species to identify which features of regeneration are initiated and which fail to be initiated in non-regenerating species. Experiments will include investigations of early wound healing (through studies of autotomy and apoptosis), blastema formation (through studies of cell proliferation, cell migration, and stem cell distribution), and early body patterning (through studies of body-patterning gene expression). Parallel investigations of several lineages that have independently lost regeneration abilities provide the opportunity to identify developmental processes that may be particularly prone to being blocked during evolution. This work is part of a young research program in an area of evolution of development, the evolution of regeneration, that is virtually unexplored and yet has the potential to uncover proximal explanations for why regeneration ability varies so dramatically among animals.The main broader impacts of this proposal are two-fold. 1) Fostering education at multiple levels: This project will promote the education of personnel at the undergraduate, graduate, and post-graduate levels. In addition to the PI fostering their training directly, personnel at different stages of their careers will have opportunities for varied types of learning and mentoring through interactions with each other. This project is exceptionally well suited to involving undergraduates, as many of the regeneration experiments can be completed in a short period of time without much training, and yet produce significant and novel results. 2) Potential relevance to human stem cell biology and regeneration: Comparative studies of regeneration ability can provide insight into why regeneration abilities vary so dramatically among different animals, a question of academic as well as medical importance. Annelids generally have extensive regeneration abilities: many species can regenerate every region of their body, including their brain, ventral nervous system, eyes, mouth, gut, muscle, etc. from only a small fraction of the original worm. Understanding why regeneration can fail even in relatively simple organisms whose very close relatives regenerate extensively may ultimately suggest avenues for fostering human regeneration.

动物通过再生能够替换失去的身体部位的能力差异很大。 拟议的工作旨在通过调查具有不同再生能力的密切相关的物种来回答两个主要问题：（1）非再生物种中哪些发育过程失败？ （2）在独立失去再生能力的不同谱系中，相同的发展过程是否失败？该提案的具体目标是确定密切相关的再生和非再生物种，表征正常早期再生的发育步骤，并确定这些步骤中的哪些步骤未在最近失去再生能力的物种中启动。比较再生实验将对NAIDINE的一组（分段）蠕虫进行研究，以研究再生能力的系统发育分布。尽管许多NAIDINE具有广泛的能力来再生其前部/后轴的一部分，但已经确定了几种物种失去了前再生的能力。将对三个前后再生物种和两个独立衍生的非自然再生物种进行更详细的发育特征，以识别启动哪些再生特征，并且在非再生物种中未启动哪些特征。实验将包括对早期伤口愈合的研究（通过自动切开术和凋亡的研究），胚泡形成（通过研究细胞增殖，细胞迁移和干细胞分布）以及早期身体模式（通过研究身体造成的基因表达）。对几个独立失去再生能力的几个谱系的平行调查为识别可能在进化过程中特别容易被阻止的发展过程提供了机会。这项工作是在发展的发展领域，再生的演变中，这实际上是没有探索的，但有可能发现为什么再生能力在动物之间如此巨大变化。 1）在多个层面上培养教育：该项目将促进本科，研究生和研究生级别的人员教育。除了PI直接培养培训外，在职业生涯的不同阶段的人员还将有机会通过彼此互动进行多种多样的学习和指导。该项目非常适合涉及本科生，因为许多再生实验可以在短时间内完成，而无需太多训练，但产生了重大和新颖的结果。 2）与人类干细胞生物学和再生的潜在相关性：再生能力的比较研究可以洞悉为什么不同动物之间的再生能力在不同的动物中如此巨大，这是学术和医学重要性的问题。 Annelids通常具有广泛的再生能力：许多物种可以再生其身体的每个区域，包括他们的大脑，腹神经系统，眼睛，嘴巴，肠道，肌肉等。理解为什么再生甚至在相对简单的生物中会失败，这些生物的亲密亲戚更广泛地再生可能最终暗示促进人类再生的途径。