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.
