The evolution of regenerative capacities in tetrapod limbs - a deep time perspective combining extant and fossil data

• Applicant: Professorin Dr. Nadia Belinda Fröbisch
• Subject Area: Palaeontology ; Evolution, Anthropology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 386259701

Salamanders are extraordinary among tetrapods because of their extremely high regenerative capacities that includes parts of internal organs, lenses of the eye, and full limb and tail regeneration. Particularly limb regeneration has been subject to intensive research and great advances have been made in the past decades, especially with respect to the molecular control of limb regeneration. The vast majority of studies on limb regeneration have used the Mexican axolotl Ambystoma mexicanum, a neotenic ambystomatid salamander, as model organism in laboratory experiments. In contrast, very little is known on the diversity of regenerative capacities within the morphologically and ecologically diverse clade of salamanders and how regeneration may differ in salamanders with life history patterns different from the axolotl. However, together with the fossil record this data can provide important insights into the evolutionary history of regenerative capacities in the tetrapod limb and aid in identifying shared versus derived pathways in regeneration. This proposal takes an integrative approach combining paleohistological data from the fossil stem lineage of modern amphibians, histological data from extant salamanders, and comparative transcriptome data to gain a multifaceted picture of the evolutionary history of limb regeneration in tetrapods. Limb regeneration will be investigated histologically and with CT imaging techniques in selected salamander taxa to assess how speed and accuracy of limb regeneration vary along ontogenetic trajectories within taxa and between taxa with different life history pathways, including neoteny, metamorphosis and direct development. A paleohistological investigation of regenerated limbs in the Permian dissorophoid Micromelerpeton will form the basis for comparison with extant salamanders with respect to tissue level organization and regenerative anomalies. Moreover, comparative transcriptome data will be used to investigate the molecular signatures of limb regeneration in larval, neotenic, and metamorphosing salamanders, as well as lungfish and frogs. The combination of the data of these approaches will provide a novel basis for our understanding of the evolutionary history of limb regeneration in tetrapods, as well as highlight future research avenues on the impact of ontogeny and life history parameters in regeneration, and potentially shifting roles of certain molecular signals (e.g. stem cell signals) in regeneration along these trajectories.

• DFG Programme: Research Grants
• International Connection: Brazil
• Cooperation Partners: Professor Dr. Igor Schneider; Dr. Florian Witzmann