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

火蜥蜴在四足动物中是非同寻常的，因为它们具有极高的再生能力，包括内脏的部分，眼睛的晶状体，以及四肢和尾巴的完全再生。尤其是肢体再生，在过去的几十年里得到了深入的研究，并取得了很大的进展，特别是在肢体再生的分子控制方面。绝大多数关于肢体再生的研究都是以墨西哥华支睾吸虫作为实验室实验的模式生物。相比之下，关于火蜥蜴在形态和生态上不同的支系中再生能力的多样性，以及生活史模式与Axolotl不同的火蜥蜴的再生可能如何不同，人们知之甚少。然而，结合化石记录，这些数据可以为四足动物肢体再生能力的进化史提供重要的见解，并有助于识别再生中共享和衍生的路径。这一建议采用了一种综合的方法，结合了现代两栖动物化石干谱系的古组织学数据、现存火蜥蜴的组织学数据和比较转录组数据，以获得四足动物肢体再生进化史的多方面图景。肢体再生将通过组织学和CT成像技术进行研究，以评估肢体再生的速度和准确性如何随分类群内的个体发育轨迹以及具有不同生活史途径的分类群之间的变化而变化，包括新生、变态和直接发育。对二叠纪蜥蜴再生肢体的古组织学研究将为与现存的火蜥蜴在组织水平组织和再生异常方面的比较奠定基础。此外，比较转录组数据将被用来研究幼体、幼体和变态火蜥蜴以及肺鱼和青蛙肢体再生的分子特征。这些方法的数据结合将为我们理解四足动物肢体再生的进化史提供新的基础，并突出显示个体发育和生活史参数在再生中的影响以及某些分子信号(如干细胞信号)在再生中的潜在角色沿这些轨迹变化的未来研究途径。

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.