The Francis Crick Institute, London, NW1 1AT, UK.
Centro de Biología Molecular Severo Ochoa (CSIC/UAM), C/Nicolás Cabrera 1, Madrid, 28049, Spain.
BMC Biol. 2024 Apr 29;22(1):98. doi: 10.1186/s12915-024-01894-1.
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 our comprehension of the regenerative potential of pupal wings and the underlying mechanisms contributing to the decline of regenerative responses remains limited.
Here, we explore 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 proliferative response can continue until 34 h after puparium formation (APF), beyond this point cell death alone is not sufficient to induce a regenerative response. Under normal circumstances, cell proliferation ceases around 24 h APF. Interestingly, the failure of reinitiating the cell cycle beyond this time point is not attributed to an incapacity to activate the JNK pathway. Instead, our results suggest that the function of the ecdysone-responsive transcription factor E93 is involved in limiting the apoptosis-induced proliferative response during pupal development.
Our study shows that apoptosis can prolong the proliferative period of cells in the wing during pupal development as late as 34 h APF, at least 10 h longer than during normal development. After this time point, the regenerative response is diminished, a process mediated in part by the ecdysone-responsive transcription factor E93.
动物再生受损组织的能力是一个复杂的过程，涉及各种细胞机制。随着动物年龄的增长，它们会失去再生能力，因此了解限制衰老过程中再生能力的潜在机制至关重要。黑腹果蝇的翅膀 imaginal discs 是上皮结构，可以在组织损伤后再生。虽然已经有大量研究集中在幼虫阶段的再生反应，但我们对蛹期翅膀的再生潜力以及导致再生反应下降的潜在机制的理解仍然有限。
在这里，我们探索了细胞死亡诱导的增殖反应在蛹发育过程中的时间动态，这是一种典型的再生反应。我们的结果表明，凋亡诱导的增殖反应可以持续到蛹形成后 34 小时（APF），在此之后，单独的细胞死亡不足以诱导再生反应。在正常情况下，细胞增殖在 24 小时 APF 左右停止。有趣的是，此时点之后无法重新启动细胞周期并非归因于无法激活 JNK 途径。相反，我们的结果表明，蜕皮激素反应转录因子 E93 的功能参与限制了蛹发育过程中凋亡诱导的增殖反应。
我们的研究表明，凋亡可以延长蛹发育过程中翅膀细胞的增殖期，直到 34 小时 APF，至少比正常发育长 10 小时。在此时间点之后，再生反应减弱，这一过程部分由蜕皮激素反应转录因子 E93 介导。
