Hans Müller, Sofia González-Mendez, Li Wei-Tao
Regeneration is a complex biological process allowing organisms to replace lost tissues and organs. The Mexican axolotl (Ambystoma mexicanum) serves as a model organism for studying limb regeneration due to its remarkable regenerative capabilities. This study aims to elucidate the molecular mechanisms that govern limb regeneration in axolotls, focusing on genetic regulation. Using RNA sequencing and CRISPR-Cas9 gene-editing technologies, we identified key regulatory genes involved in the early stages of regeneration. Our findings highlight the upregulation of genes associated with the Wnt/β-catenin signaling pathway, including Axin2 and Lef1, which showed a significant increase in expression levels (p < 0.01) during the dedifferentiation phase. Additionally, we observed the critical role of miRNA-133 in modulating the proliferation of blastemal cells. These results suggest that limb regeneration in axolotls involves a concerted action of multiple genetic pathways, with potential implications for regenerative medicine. This research contributes to the understanding of vertebrate regeneration and may lay the groundwork for developing therapeutic strategies to enhance regenerative responses in humans. Further investigations are warranted to explore the interplay between these identified pathways and their potential cross-talk with other cellular processes.