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bioRxiv · 10.1101/724260

NF-κB signaling regulates the formation of proliferating Muller glia-derived progenitor cells in the avian retina.

Palazzo, I.·Deistler, K.·Hoang, T. V.·Blackshaw, S.·Fischer, A. J.
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Abstract

Neuronal 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 Muller 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 Muller 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-{kappa}B) signaling, a critical regulator of inflammation. We find that components of the NF-{kappa}B pathway are expressed by Muller glia and are dynamically regulated after neuronal damage or treatment with growth factors. Inhibition of NF-{kappa}B enhances, whereas activation suppresses the formation of proliferating MGPCs. Additionally, activation of NF-{kappa}B promotes glial differentiation from MGPCs in damaged retinas. With microglia ablated, the effects of NF-{kappa}B-agonists/antagonists on MGPC formation are reversed, suggesting that the context and timing of signals provided by reactive microglia influence how NF-{kappa}B-signaling impacts the reprogramming of Muller glia. We propose that NF-{kappa}B-signaling is an important signaling \"hub\" that suppresses the reprogramming of Muller glia into proliferating MGPCs and this \"hub\" coordinates signals provided by reactive microglia.

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Palazzo, I., Deistler, K., Hoang, T. V., Blackshaw, S., Fischer, A. J.. 2019-08-02. NF-κB signaling regulates the formation of proliferating Muller glia-derived progenitor cells in the avian retina.. https://doi.org/10.1101/724260

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