Mechanisms of regeneration: to what extent do they recapitulate development?

Abstract

One of the enduring debates in regeneration biology is the degree to which regeneration mirrors development. Recent technical advances, such as single-cell transcriptomics and the broad applicability of CRISPR systems, coupled with new model organisms in research, have led to the exploration of this longstanding concept from a broader perspective. In this Review, I outline the historical parallels between development and regeneration before focusing on recent research that highlights how dissecting the divergence between these processes can uncover previously unreported biological mechanisms. Finally, I discuss how these advances position regeneration as a more dynamic and variable process with expanded possibilities for morphogenesis compared with development. Collectively, these insights into mechanisms that orchestrate morphogenesis may reshape our understanding of the evolution of regeneration, reveal hidden biology activated by injury, and offer non-developmental strategies for restoring lost or damaged organs and tissues.