Evolution of regeneration: a comparative study in annelids

动物通过再生来替换失去的身体部位的能力差异很大。 这项工作的目的是回答两个主要问题，通过调查密切相关的物种具有不同的再生能力：（1）哪些发展过程中失败的非再生物种？(2)相同的发育过程在独立失去再生能力的不同谱系中是否会失败？本提案的具体目标是识别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不能在最近失去再生能力的物种中启动。比较再生实验将进行一组环节动物（分节）蠕虫，naidines，研究再生能力的系统发育分布。虽然许多奈丁类动物有广泛的能力再生部分前/后体轴，但已经确定了几个物种已经失去了前再生的能力。更详细的发育特征将进行三个前再生物种和两个独立衍生的nonanteriorly再生物种，以确定哪些功能的再生启动，哪些不启动在非再生物种。实验将包括早期伤口愈合的调查（通过自切和凋亡的研究），芽基形成（通过细胞增殖，细胞迁移和干细胞分布的研究），和早期身体图案（通过身体图案基因表达的研究）。平行调查的几个谱系，独立失去再生能力提供了机会，以确定可能是特别容易被阻止在进化过程中的发展过程。这项工作是一个年轻的研究计划的一部分，在一个领域的发展，再生的进化，这是几乎未被探索，但有可能揭示最近的解释为什么再生能力差异如此显着的动物。1)促进多层次教育：该项目将促进本科生、研究生和研究生一级的人员教育。除了PI直接促进他们的培训外，处于职业生涯不同阶段的人员将有机会通过相互交流进行各种类型的学习和指导。这个项目非常适合本科生参与，因为许多再生实验可以在短时间内完成，而无需太多培训，但会产生重大而新颖的结果。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，腹神经系统，眼睛，嘴巴，肠道，肌肉等。了解为什么再生可以失败，即使在相对简单的生物体，其非常密切的亲戚再生广泛可能最终建议促进人类再生的途径。

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.