Bose Anish, Schuster Keaton, Kodali Chandril, Sonam Surabhi, Smith-Bolton Rachel K
Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Sci Adv. 2025 Jun 6;11(23):eads5743. doi: 10.1126/sciadv.ads5743.
Many animals can regenerate tissues after injury. While the initiation of regeneration has been studied extensively, how the damage response ends and normal gene expression returns is unclear. We found that in wing imaginal discs, the pioneer transcription factor Zelda controls the exit from regeneration and return to normal gene expression. Optogenetic inactivation of Zelda during regeneration disrupted patterning, induced cell fate errors, and caused morphological defects yet had no effect on normal wing development. Using Cleavage Under Targets & Release Using Nuclease, we identified targets of Zelda important for the end of regeneration, including genes that control wing margin and vein specification, compartment identity, and cell adhesion. We also found that GAGA factor and Fork head similarly coordinate patterning after regeneration and that chromatin regions bound by Zelda increase in accessibility during regeneration. Thus, Zelda orchestrates the transition from regeneration to normal gene expression, highlighting a fundamental difference between developmental and regeneration patterning in the wing disc.
许多动物在受伤后能够再生组织。虽然再生的起始过程已得到广泛研究，但损伤反应如何结束以及正常基因表达如何恢复尚不清楚。我们发现，在翅成虫盘（wing imaginal discs）中，先驱转录因子Zelda控制着再生的终止以及向正常基因表达的恢复。在再生过程中对Zelda进行光遗传学失活会破坏模式形成，诱导细胞命运错误，并导致形态缺陷，但对正常翅发育没有影响。使用核酸酶靶向切割与释放技术（Cleavage Under Targets & Release Using Nuclease），我们鉴定出了对再生结束至关重要的Zelda靶标，包括控制翅边缘和翅脉特化、区域身份以及细胞黏附的基因。我们还发现，GAGA因子和叉头蛋白（Fork head）在再生后同样协调模式形成，并且在再生过程中Zelda结合的染色质区域的可及性增加。因此，Zelda精心协调从再生到正常基因表达的转变，突出了翅成虫盘中发育模式形成和再生模式形成之间的根本差异。
