Tgf-β signaling is a major antiproliferative pathway governing different biological functions, including cellular reprogramming. Upon injury, Müller glial cells of zebrafish retina reprogram to form progenitors (MGPCs) essential for regeneration. Here, the significance of Tgf-β signaling for inducing MGPCs is explored. Notably, Tgf-β signaling not only performs a pro-proliferative function but also is necessary for the expression of several regeneration-associated, essential transcription factor genes such as ascl1a, lin28a, oct4, sox2, and zebs and various microRNAs, namely, miR-200a, miR-200b, miR-143, and miR-145 during different phases of retinal regeneration. This study also found the indispensable role played by Mmp2/Mmp9 in the efficacy of Tgf-β signaling. Furthermore, the Tgf-β signaling is essential to cause cell cycle exit of MGPCs towards later phases of regeneration. Finally, the Delta-Notch signaling in collaboration with Tgf-β signaling regulates the critical factor, Her4.1. This study provides novel insights into the biphasic roles of Tgf-β signaling in zebrafish during retinal regeneration.

Tgf-β 信号传导是控制不同生物学功能（包括细胞重编程）的主要抗增殖途径。受伤后，斑马鱼视网膜的 Müller 神经胶质细胞会重新编程，形成再生所必需的祖细胞 (MGPC)。在这里，探讨了 Tgf-β 信号传导对诱导 MGPC 的意义。值得注意的是，Tgf-β 信号不仅具有促增殖功能，而且对于几种再生相关的必需转录因子基因（如ascl1a、lin28a、oct4、sox2和zeb s 以及各种 microRNA）的表达也是必需的，即，miR-200a、miR-200b、miR-143和miR-145在视网膜再生的不同阶段。该研究还发现了 Mmp2/Mmp9 在 Tgf-β 信号传导的功效中所起的不可或缺的作用。此外，Tgf-β 信号传导对于导致 MGPC 细胞周期退出到再生的后期阶段是必不可少的。最后，Delta-Notch 信号与 Tgf-β 信号协同调节关键因子 Her4.1。这项研究为斑马鱼视网膜再生过程中TGF-β信号的双相作用提供了新的见解。