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.

动物通过再生来替换失去的身体部位的能力差别很大。本研究旨在通过研究具有不同再生能力的近亲物种来回答两个主要问题：(1)哪些发育过程在非再生物种中失败？(2)相同的发育过程是否在不同的谱系中失败，而这些谱系独立地失去了再生能力？本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，并确定哪些步骤在最近失去再生能力的物种中未能启动。比较再生实验将进行一组环节动物（节段）蠕虫，naidines，以研究再生能力的系统发育分布。虽然许多生物具有广泛的再生前/后体轴的能力，但已经发现一些物种已经失去了前体轴再生的能力。更详细的发育特征将在三个前再生物种和两个独立衍生的非前再生物种上进行，以确定哪些再生特征在非再生物种中被启动，哪些未被启动。实验将包括研究早期伤口愈合（通过研究自体切开术和细胞凋亡）、胚泡形成（通过研究细胞增殖、细胞迁移和干细胞分布）和早期身体模式（通过研究身体模式基因表达）。对几个独立失去再生能力的谱系进行平行研究，为确定在进化过程中可能特别容易被阻止的发育过程提供了机会。这项工作是一个年轻的研究项目的一部分，该项目是在一个发展的进化领域，即再生的进化，这个领域几乎没有被探索过，但有可能揭示为什么再生能力在动物之间差异如此之大的近距离解释。这一提议的主要影响有两个方面。1)培养多层次人才：本项目将促进本科、研究生、研究生三个层次的人才培养。除了PI直接指导他们的培训外，处于职业生涯不同阶段的人员将有机会通过相互互动进行各种类型的学习和指导。这个项目特别适合本科生参与，因为许多再生实验可以在短时间内完成，而不需要太多的训练，但却产生了重要的和新颖的结果。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深入了解为什么不同动物的再生能力差异如此之大，这是一个具有学术和医学重要性的问题。环节动物通常具有广泛的再生能力：许多物种可以从原始蠕虫的一小部分再生身体的每个区域，包括大脑、腹侧神经系统、眼睛、嘴巴、肠道、肌肉等。理解为什么即使是相对简单的生物体，其近亲也能广泛再生，却不能再生，可能最终为促进人类再生提供途径。