Stage-resolved analysis of posterior regeneration in Ophryotrocha labronica reveals early pluripotency activation and conserved regenerative programs

Background Regeneration is a widespread post-embryonic process across metazoans and particularly diverse among annelids, offering a valuable system to explore how complex tissues are restored and why regenerative capacity varies across species. While morphological aspects of regeneration, including nervous system reconstruction, have been extensively described, the underlying cellular and molecular mechanisms remain poorly resolved in many non-model annelids, particularly at stage-specific resolution. Results Here, we characterise posterior regeneration in the dorvilleid annelid Ophryotrocha labronica by integrating morphological, cellular, neuroanatomical, and transcriptomic approaches. We define a temporal framework from wound healing to complete tail regeneration within five days, focusing on mid-early proliferative and differentiation stages. Proliferation and stem cell-related genes contribute to blastema formation and early differentiation, while neurogenesis-related genes activate shortly after injury and persist throughout regeneration, suggesting a sustained role in coordinating blastema development. This process involves both local and migratory proliferative cells, preceded by early activation of pluripotency and neural markers. Comparative analyses further reveal both conserved and lineage-specific mechanisms in O. labronica , highlighting shared molecular pathways as well as evolutionary divergence across annelids. Conclusions Our results provide stage-resolved insights into the molecular regulation of posterior regeneration in O. labronica . Conserved signalling pathways (Notch, Hedgehog, Wnt) alongside candidates such as NOX2/CYBB, previously described in vertebrate regeneration, highlight shared and lineage-specific mechanisms underlying regenerative diversity. These findings underscore the value of non-model annelids for understanding the evolution and diversity of regenerative strategies across metazoans.