scholarly journals mTor signaling is required for the formation of proliferating Müller glia-derived progenitor cells in the chick retina

Development ◽  
2016 ◽  
Vol 143 (11) ◽  
pp. 1859-1873 ◽  
Author(s):  
Christopher P. Zelinka ◽  
Leo Volkov ◽  
Zachary A. Goodman ◽  
Levi Todd ◽  
Isabella Palazzo ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Mtor Signaling ◽  
Muller Glia ◽  
Müller Glia ◽  
Chick Retina

scholarly journals NF-κB signaling regulates the formation of proliferating Müller glia-derived progenitor cells in the avian retina

2019 ◽  
Author(s):  
Isabella Palazzo ◽  
Kyle Deistler ◽  
Thanh V. Hoang ◽  
Seth Blackshaw ◽  
Andy J. Fischer
Keyword(s):  
Progenitor Cells ◽  
Nuclear Factor Kappa B ◽  
Neuronal Damage ◽  
Muller Glia ◽  
Müller Glia ◽  
Reactive Microglia ◽  
Chick Retina ◽  
Cell Signaling Pathways

AbstractNeuronal regeneration in the retina is a robust, effective process in some cold-blooded vertebrates, but this process is ineffective in warm-blooded vertebrates. Understanding the mechanisms and cell-signaling pathways that restrict the reprogramming of Müller glia into proliferating neurogenic progenitors is key to harnessing the regenerative potential of the retina. Inflammation and reactive microglia are known to influence the formation of Müller glia-derived progenitor cells (MGPCs), but the mechanisms underlying this response are unknown. Using the chick retina in vivo as a model system, we investigate the role of the Nuclear Factor kappa B (NF-κB) signaling, a critical regulator of inflammation. We find that components of the NF-κB pathway are expressed by Müller glia and are dynamically regulated after neuronal damage or treatment with growth factors. Inhibition of NF-κB enhances, whereas activation suppresses the formation of proliferating MGPCs. Additionally, activation of NF-κB promotes glial differentiation from MGPCs in damaged retinas. With microglia ablated, the effects of NF-κB-agonists/antagonists on MGPC formation are reversed, suggesting that the context and timing of signals provided by reactive microglia influence how NF-κB-signaling impacts the reprogramming of Müller glia. We propose that NF-κB-signaling is an important signaling “hub” that suppresses the reprogramming of Müller glia into proliferating MGPCs and this “hub” coordinates signals provided by reactive microglia.

scholarly journals Nuclear Factor I in neurons, glia and during the formation of Muller glia-derived progenitor cells in avian, porcine and primate retinas

2021 ◽  
Author(s):  
Heithem El-Hodiri ◽  
Warren Campbell ◽  
Lisa Kelly ◽  
Evan Hawthorn ◽  
Maura Schwartz ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Mouse Retina ◽  
Nuclear Factor ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Neurons ◽  
Intrinsic Factors ◽  
Factor I ◽  
Chick Retina ◽  
Nuclear Factor I

The regenerative potential of Müller glia (MG) is extraordinary in fish, poor in chick and terrible in mammals. In the chick model, MG readily reprogram into proliferating Müller glia-derived progenitor cells (MGPCs), but neuronal differentiation is very limited. The factors that suppress the neurogenic potential of MGPCs in the chick are slowly being revealed. Isoforms of Nuclear Factor I (NFI) are cell-intrinsic factors that limit neurogenic potential; these factors are required for the formation of MG in the developing mouse retina (Clark et al., 2019) and deletion of these factors reprograms MG into neuron-like cells in mature mouse retina (Hoang et al., 2020). Accordingly, we sought to characterize the patterns of expression NFIs in the developing, mature and damaged chick retina. In addition, we characterized patterns of expression of NFIs in the retinas of large mammals, pigs and monkeys. Using a combination of single cell RNA-sequencing (scRNA-seq) and immunolabeling we probed for patterns of expression. In embryonic chick, levels of NFIs are very low in early E5 (embryonic day 5) retinal progenitor cells (RPCs), up-regulated in E8 RPCs, further up-regulated in differentiating MG at E12 and E15. NFIs are maintained in mature resting MG, microglia and neurons. Levels of NFIs are reduced in activated MG in retinas treated with NMDA and/or insulin+FGF2, and further down-regulated in proliferating MGPCs. However, levels of NFIs in MGPCs were significantly higher than those seen in RPCs. Immunolabeling for NFIA and NFIB closely matched patterns of expression revealed in different types of retinal neurons and glia, consistent with findings from scRNA-seq. In addition, we find expression of NFIA and NFIB through progenitors in the circumferential marginal zone at the far periphery of the retina. We find similar patterns of expression for NFIs in scRNA-seq databases for pig and monkey retinas. Patterns of expression of NFIA and NFIB were validated with immunofluorescence in pig and monkey retinas wherein these factors were predominantly detected in MG and a few types of inner retinal neurons. In summary, NFIA and NFIB are prominently expressed in developing chick retina and by mature neurons and glia in the retinas of chicks, pigs and monkeys. Although levels of NFIs are decreased in chick, in MGPCs these levels remain higher than those seen in neurogenic RPCs. We propose that the neurogenic potential of MGPCs in the chick retina is suppressed by NFIs.

scholarly journals NF-κB signaling regulates the formation of proliferating Müller glia-derived progenitor cells in the avian retina

Development ◽  
2020 ◽  
Vol 147 (10) ◽  
pp. dev183418 ◽  
Author(s):  
Isabella Palazzo ◽  
Kyle Deistler ◽  
Thanh V. Hoang ◽  
Seth Blackshaw ◽  
Andy J. Fischer
Keyword(s):  
Progenitor Cells ◽  
Muller Glia ◽  
Müller Glia ◽  
Avian Retina

scholarly journals Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

2015 ◽  
Vol 76 (9) ◽  
pp. 983-1002 ◽  
Author(s):  
Donika Gallina ◽  
Isabella Palazzo ◽  
Lillia Steffenson ◽  
Levi Todd ◽  
Andy J. Fischer
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Chick Retina

scholarly journals BMP- and TGFβ-signaling regulate the formation of Müller glia-derived progenitor cells in the avian retina

Glia ◽  
2017 ◽  
Vol 65 (10) ◽  
pp. 1640-1655 ◽  
Author(s):  
Levi Todd ◽  
Isabella Palazzo ◽  
Natalie Squires ◽  
Ninoshka Mendonca ◽  
Andy J. Fischer
Keyword(s):  
Progenitor Cells ◽  
Muller Glia ◽  
Müller Glia ◽  
Tgfβ Signaling ◽  
Avian Retina

scholarly journals Potential of Müller glia to become neurogenic retinal progenitor cells

Glia ◽  
2003 ◽  
Vol 43 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Andy J. Fischer ◽  
Thomas A. Reh
Keyword(s):  
Progenitor Cells ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Progenitor Cells ◽  
Retinal Progenitor
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