Impact of transposable elements during animal regeneration

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Regeneration capabilities vary significantly across multicellular organisms. Studies on the underlying molecular mechanisms and their evolution have largely focused on deciphering the coding gene complement in various model systems with studies of the non-coding genome recently coming into focus. Transposable elements (transposons) comprise the largest portion of the non-coding sequence. Recent data shows that specific transposons are activated during regeneration. Interestingly, on an evolutionary time-scale, transposons can contribute to the characteristic large genome size of many species with extraordinary regeneration capabilities. This is a result of both elevated activity and insertion rate of transposons, cellular defenses against their insertions or deletions, as well as the given population structure and selective pressures that in the long time-scale balances their maintenance or deletion. Combined with their known role in genome stability and generation of regulatory novelty those insights pose key yet still unanswered questions regarding the role of transposons both during the actual process of regeneration as well as a potential evolutionary drive to evolve sophisticated regenerative capabilities.This proposal will compare the transcriptional dynamics of transposons during regeneration and their effect on the genome architecture in two key, phylogenetically informative model systems for regeneration, the cnidarian Hydra magnipapillata and the vertebrate, salamander, Ambystoma mexicanum (axolotl). We will characterize the shared and derived transcriptionally active transposable elements among those two species, providing the first complete overview of regeneration-active elements at the sub-family resolution level. We will then study cellular-level activity of transposons in regenerating tissues and functionally test their role in vivo. We will finally study genome-wide transposon insertion dynamics in consecutively regenerating tissues, such as in the repeated cycles of regeneration during dissociation-reaggregation experiments in hydra or consecutive limb regeneration in axolotl. This experiment will allow us to investigate, on the genome-wide scale, transposon insertion patterns and their effect on core genes involved in injury response and tissue regeneration.Such data will reveal, for the first time, the functional repertoire of transposons during regeneration and the extent to which the genomes are affected during each regenerative cycle, encompassing both developmental and evolutionary time-scales. The data will provide crucial insights into the genome stability, response, as well as modifications to its structure such as the presence of any regeneration-linked hotspots in the genome.