Bose Anish, Schuster Keaton, Kodali Chandril, Sonam Surabhi, Smith-Bolton Rachel
Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
bioRxiv. 2024 May 30:2024.05.30.596672. doi: 10.1101/2024.05.30.596672.
For a damaged tissue to regenerate, the injured site must repair the wound, proliferate, and restore the correct patterning and cell types. We found that Zelda, a pioneer transcription factor largely known for its role in embryonic zygotic genome activation, is dispensable for normal wing development but crucial for wing disc patterning during regeneration. Impairing Zelda function during disc regeneration resulted in adult wings with a plethora of cell fate errors, affecting the veins, margins, and posterior compartment identity. Using CUT&RUN, we identified and validated targets of Zelda including the cell fate genes and , which failed to return to their normal expression patterns upon loss of Zelda. In addition, Zelda controls expression of factors previously established to preserve cell fate during regeneration like and which stabilizes expression during regeneration, thereby preserving posterior identity. Finally, Zelda ensures proper expression of the integrins encoded by and during regeneration to prevent blisters in the resuting adult wing. Thus, Zelda is crucial for maintaining cell fate and structural architecture of the regenerating tissue.
对于受损组织的再生,受伤部位必须修复伤口、增殖并恢复正确的模式和细胞类型。我们发现,Zelda是一种先驱转录因子,主要因其在胚胎合子基因组激活中的作用而闻名,它对于正常的翅膀发育并非必需,但对于再生过程中翅芽的模式形成至关重要。在翅芽再生过程中削弱Zelda的功能会导致成年翅膀出现大量细胞命运错误,影响翅脉、边缘和后区特征。通过CUT&RUN技术,我们鉴定并验证了Zelda的靶标,包括细胞命运基因 和 ,在缺失Zelda后它们无法恢复到正常表达模式。此外,Zelda控制先前确定的在再生过程中维持细胞命运的因子的表达,如 和 ,后者在再生过程中稳定 表达,从而维持后区特征。最后,Zelda确保在再生过程中由 和 编码的整合素的正确表达,以防止成年翅膀出现水泡。因此,Zelda对于维持再生组织的细胞命运和结构架构至关重要。