Application of Comparative Functional Genomics to Identify Regeneration-Specific Genes.

摘要

This project proposes novel and unbiased genomic approaches to identify genes associated with salamander limb regeneration. The first objective will extend an ongoing study of the transcriptional basis of limb regeneration in the Mexican axolotl (Ambystoma mexicanum) to three additional salamander species (A. tigrinum, A. maculatum, and Notophthalmus viridescens). Transcripts will be sampled at four times during limb regeneration to characterize temporal changes in abundance that coincide with wound healing and blastema formation. Accomplishment of this objective will enhance an ongoing DOD Multi-Investigator Research Initiative by resolving genes and molecular pathways for translation to mammalian injury models. The second objective will use quantitative trait locus (QTL) mapping and a newly derived salamander line to identify genes that contribute to variation in limb regeneration. Genotypic and statistical approaches will be used to identify genotype-phenotype associations indicative of QTL for regeneration traits. Accomplishment of this objective will set the stage for identifying loci that explain genetic and developmental sources of variation during limb regeneration. Overall, the project is significant because novel approaches will be used to reveal fundamental regenerative processes that could be engineered in humans to dramatically improve the quality and length of life after injury.