scholarly journals Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration

Cell Reports ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. 272-284 ◽  
Author(s):  
Xiao-Feng Zhao ◽  
Jin Wan ◽  
Curtis Powell ◽  
Rajesh Ramachandran ◽  
Martin G. Myers ◽  
...  
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Retina Regeneration

scholarly journals Tgfb3 collaborates with PP2A and notch signaling pathways to inhibit retina regeneration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mi-Sun Lee ◽  
Jin Wan ◽  
Daniel Goldman
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Neuronal Degeneration ◽  
Muller Glia ◽  
Müller Glia ◽  
Retina Regeneration ◽  
Retinal Injury ◽  
Multipotent Progenitors ◽  
Tgfb Signaling

Neuronal degeneration in the zebrafish retina stimulates Müller glia (MG) to proliferate and generate multipotent progenitors for retinal repair. Controlling this proliferation is critical to successful regeneration. Previous studies reported that retinal injury stimulates pSmad3 signaling in injury-responsive MG. Contrary to these findings, we report pSmad3 expression is restricted to quiescent MG and suppressed in injury-responsive MG. Our data indicates that Tgfb3 is the ligand responsible for regulating pSmad3 expression. Remarkably, although overexpression of either Tgfb1b or Tgfb3 can stimulate pSmad3 expression in the injured retina, only Tgfb3 inhibits injury-dependent MG proliferation; suggesting the involvement of a non-canonical Tgfb signaling pathway. Furthermore, inhibition of Alk5, PP2A or Notch signaling rescues MG proliferation in Tgfb3 overexpressing zebrafish. Finally, we report that this Tgfb3 signaling pathway is active in zebrafish MG, but not those in mice, which may contribute to the different regenerative capabilities of MG from fish and mammals.

scholarly journals Histone Deacetylase-Mediated Müller Glia Reprogramming through Her4.1-Lin28a Axis Is Essential for Retina Regeneration in Zebrafish

iScience ◽  
2018 ◽  
Vol 7 ◽  
pp. 68-84 ◽  
Author(s):  
Soumitra Mitra ◽  
Poonam Sharma ◽  
Simran Kaur ◽  
Mohammad Anwar Khursheed ◽  
Shivangi Gupta ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Muller Glia ◽  
Müller Glia ◽  
Retina Regeneration

scholarly journals Oct4 mediates Müller glia reprogramming and cell cycle exit during retina regeneration in zebrafish

2019 ◽  
Vol 2 (5) ◽  
pp. e201900548 ◽  
Author(s):  
Poonam Sharma ◽  
Shivangi Gupta ◽  
Mansi Chaudhary ◽  
Soumitra Mitra ◽  
Bindia Chawla ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cellular Reprogramming ◽  
Muller Glia ◽  
Cell Cycle Exit ◽  
Müller Glia ◽  
Nucleosome Remodeling ◽  
Retina Regeneration ◽  
Inducing Factors ◽  
Transcription Factor 4 ◽  
Factor Governing

Octamer-binding transcription factor 4 (Oct4, also known as Pou5F3) is an essential pluripotency-inducing factor, governing a plethora of biological functions during cellular reprogramming. Retina regeneration in zebrafish involves reprogramming of Müller glia (MG) into a proliferating population of progenitors (MGPCs) with stem cell–like characteristics, along with up-regulation of pluripotency-inducing factors. However, the significance of Oct4 during retina regeneration remains elusive. In this study, we show an early panretinal induction of Oct4, which is essential for MG reprogramming through the regulation of several regeneration-associated factors such as Ascl1a, Lin28a, Sox2, Zeb, E-cadherin, and various miRNAs, namely, let-7a, miR-200a/miR-200b, and miR-143/miR-145. We also show the crucial roles played by Oct4 during cell cycle exit of MGPCs in collaboration with members of nucleosome remodeling and deacetylase complex such as Hdac1. Notably, Oct4 regulates Tgf-β signaling negatively during MG reprogramming, and positively to cause cycle exit of MGPCs. Our study reveals unique mechanistic involvement of Oct4, during MG reprogramming and cell cycle exit in zebrafish, which may also account for the inefficient retina regeneration in mammals.

scholarly journals Temporal regulation of Pten is essential for retina regeneration in zebrafish

2021 ◽  
Author(s):  
Shivangi Gupta ◽  
Poonam Sharma ◽  
Mansi Choudhary ◽  
Sharanya Premraj ◽  
Simran Kaur ◽  
...  
Keyword(s):  
Cell Types ◽  
Acute Injury ◽  
Retinal Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Phosphatase And Tensin Homolog ◽  
Temporal Regulation ◽  
Retina Regeneration ◽  
Tensin Homolog ◽  
Ability To Regenerate

Unlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia-derived progenitor cells (MGPCs) exhibiting stem cell-like characteristics, which are capable of restoring all retinal cell-types. Here, we explored the importance of Phosphatase and tensin homolog (Pten), a dual-specificity phosphatase and tumor suppressor during retina regeneration. The Pten undergo rapid downregulation in the Müller glia and is absent in MGPCs, which is essential to trigger Akt-mediated cell proliferation to cause retina regeneration. We found that the forced downregulation of Pten accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9-activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that Pten expression is fine-tuned through Mycb/histone deacetylase1 and Tgf-β signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.

scholarly journals The miR-216a-Dot1l Regulatory Axis Is Necessary and Sufficient for Müller Glia Reprogramming during Retina Regeneration

Cell Reports ◽  
2019 ◽  
Vol 28 (8) ◽  
pp. 2037-2047.e4 ◽  
Author(s):  
Nergis Kara ◽  
Matthew R. Kent ◽  
Dominic Didiano ◽  
Kamya Rajaram ◽  
Anna Zhao ◽  
...  
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Retina Regeneration ◽  
Necessary And Sufficient

scholarly journals miRNAs and Müller Glia Reprogramming During Retina Regeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Gregory J. Konar ◽  
Claire Ferguson ◽  
Zachary Flickinger ◽  
Matthew R. Kent ◽  
James G. Patton
Keyword(s):  
Chromatin Accessibility ◽  
Model Systems ◽  
Signaling Cascades ◽  
Small Subset ◽  
Muller Glia ◽  
Müller Glia ◽  
Key Factors ◽  
Genetic Pathways ◽  
Retina Regeneration ◽  
Gene Regulatory

The use of model systems that are capable of robust, spontaneous retina regeneration has allowed for the identification of genetic pathways and components that are required for retina regeneration. Complemented by mouse models in which retina regeneration can be induced after forced expression of key factors, altered chromatin accessibility, or inhibition of kinase/signaling cascades, a clearer picture of the key regulatory events that control retina regeneration is emerging. In all cases, Müller glia (MG) serve as an adult retinal stem cell that must be reprogrammed to allow for regeneration, with the end goal being to understand why regenerative pathways are blocked in mammals, but spontaneous in other vertebrates such as zebrafish. miRNAs have emerged as key gene regulatory molecules that control both development and regeneration in vertebrates. Here, we focus on a small subset of miRNAs that control MG reprogramming during retina regeneration and have the potential to serve as therapeutic targets for treatment of visual disorders and damage.

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