Temporal Dynamics of Apoptosis-Induced Proliferation in Pupal Wing Development: Implications for Regenerative Ability

Abstract

The ability of animals to regenerate damaged tissue is a complex process that involves various cellular mechanisms. As animals age, they lose their regenerative abilities, making it essential to understand the underlying mechanisms that limit regenerative ability during aging. Drosophila melanogaster wing imaginal discs are epithelial structures that can regenerate after tissue injury. While significant research has focused on investigating regenerative responses during larval stages, particularly regarding the regulation and function of the JNK pathway, our comprehension of the regenerative potential of pupal wings and the underlying mechanisms contributing to the decline of regenerative responses remains limited. This study explores the temporal dynamics during pupal development of the proliferative response triggered by the induction of cell death, a typical regenerative response. Our results indicate that the apoptosis-induced proliferation response can be initiated as late as 30 hours after pupa formation (APF), when in normal circumstances cell proliferation ceases at around 20 hours APF. Furthermore, our data revealed that after 35 hours APF, cell death alone fails to induce further proliferation. Interestingly, the failure of reinitiating the cell cycle beyond this time point is not attributed to an incapacity to activate the JNK pathway. Instead, one of the constraining factors in the apoptotic-induced proliferation process during pupal development seems to be the activity level of ecdysone-responsive genes. Author SummaryAnimals have the remarkable ability to regenerate damaged tissues, but this regenerative potential diminishes with age. Understanding the mechanisms underlying age-related decline in regenerative abilities is crucial. Drosophila melanogaster wing imaginal discs provide a valuable model for studying tissue regeneration. While significant research has focused on regenerative responses during larval stages, our understanding of the regenerative potential and mechanisms in pupal wings remains limited. In this study, we investigate the temporal dynamics of the proliferative response triggered by cell death during late during the development, in pupal development. Our findings reveal that the apoptosis-induced proliferation response can occur during pupal development, even after normal cell proliferation has ceased. However, at late stages of pupal development this response does not occur. We have found that, the inability to reinitiate the cell cycle beyond this time point is influenced by the activity of the hormone ecdysone and its-responsive genes. These findings shed light on the dynamic processes involved in tissue regeneration during pupal development. This study expands our understanding of the complex interplay between cell death, proliferation, and gene activity during tissue regeneration, providing valuable insights for future research in regenerative biology.