BMP- and TGF[beta]-signaling regulate the formation of Muller glia-derived progenitor cells in the avian retina

Muller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGF[beta]/Smad2/3-sig...

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Bibliographic Details
Published in:Glia 2017-10, Vol.65 (10), p.1640
Main Authors: Todd, Levi, Palazzo, Isabella, Squires, Natalie, Mendonca, Ninoshka, Fischer, Andy J
Format: Article
Language:English
Subjects:
Cells (biology)
Cytoplasm
Damage
Fibroblast growth factor 2
Glial stem cells
Inhibition
N-Methyl-D-aspartic acid
Neuronal-glial interactions
Nuclei
Retina
Signal transduction
Smad protein
Smad2 protein
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Summary:Muller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGF[beta]/Smad2/3-signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8 is selectively up-regulated in the nuclei of Muller glia following treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is blocked by a dorsomorphin analogue DMH1. By comparison, Smad2/3 is found in the nuclei of Muller glia in untreated retinas, and becomes localized to the cytoplasm following NMDA- or FGF2-treatment. These findings suggest a decrease in TGF[beta]- and increase in BMP-signaling when MGPCs are known to form. In both NMDA-damaged and FGF2-treated retinas, inhibition of BMP-signaling suppressed the proliferation of MGPCs, whereas inhibition of TGF[beta]-signaling stimulated the proliferation of MGPCs. Consistent with these findings, TGF[beta]2 suppressed the formation of MGPCs in NMDA-damaged retinas. Our findings indicate that BMP/TGF[beta]/Smad-signaling is recruited into the network of signaling pathways that controls the formation of proliferating MGPCs. We conclude that signaling through BMP4/Smad1/5/8 promotes the formation of MGPCs, whereas signaling through TGF[beta]/Smad2/3 suppresses the formation of MGPCs.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.23185