Sharma Poonam, Gupta Shivangi, Chaudhary Mansi, Mitra Soumitra, Chawla Bindia, Khursheed Mohammad Anwar, Saran Navnoor Kaur, Ramachandran Rajesh
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, Knowledge City, SAS Nagar, Sector 81, Manauli PO, Mohali, Punjab 140306, India.
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, Knowledge City, SAS Nagar, Sector 81, Manauli PO, Mohali, Punjab 140306, India.
iScience. 2020 Feb 21;23(2):100817. doi: 10.1016/j.isci.2019.100817. Epub 2020 Jan 7.
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.
转化生长因子-β（Tgf-β）信号通路是一条主要的抗增殖信号通路，调控包括细胞重编程在内的多种生物学功能。在受到损伤时，斑马鱼视网膜的穆勒胶质细胞会重编程形成再生所必需的祖细胞（MGPCs）。在此，我们探究了Tgf-β信号通路在诱导MGPCs形成过程中的重要性。值得注意的是，Tgf-β信号通路不仅具有促进增殖的功能，而且在视网膜再生的不同阶段，对于一些与再生相关的关键转录因子基因（如ascl1a、lin28a、oct4、sox2和zebs）以及多种微小RNA（即miR-200a、miR-200b、miR-143和miR-145）的表达也是必需的。本研究还发现基质金属蛋白酶2/基质金属蛋白酶9（Mmp2/Mmp9）在Tgf-β信号通路的效能中发挥着不可或缺的作用。此外，Tgf-β信号通路对于促使MGPCs在再生后期退出细胞周期至关重要。最后，Delta-Notch信号通路与Tgf-β信号通路协同调节关键因子Her4.1。本研究为Tgf-β信号通路在斑马鱼视网膜再生过程中的双相作用提供了新的见解。
