We leverage two genetically tractable salamander models, the axolotl (Ambystoma mexicanum) and the Iberian ribbed newt (Pleurodeles waltl), to uncover fundamental principles of regeneration
Regulation of cellular plasticity during regeneration
The ability of salamander tissues to undergo changes in their differentiated state to generate regenerative progenitors is thought to be at the core of the regeneration process. However there is as yet poor understanding of the molecular mechanisms behind this. In the context of the limb, we have identified a network of molecular processes required for eliciting dedifferentiation including the regulation of p53 and MAPK activation. At the cellular level, we identified senescent cells as promoters of dedifferentiation and progenitor cell expansion in newts and axolotls respectively. Recently, we uncovered a determinant of positional identity during limb regeneration, Tig1: a molecule able to reprogram the entire transcriptional network of blastema progenitors towards proximal fates, whose activity is essential for proper limb regeneration. Currently, we are expanding the investigation of cellular and molecular factors involved in the regulation of cell plasticity during regeneration of complex structures using both in vitro and in vivo functional approaches, as well as comparative analysis between regenerative and non-regenerative systems.