Jak/Stat signaling regulates the proliferation and neurogenic potential of Müller glia-derived progenitor cells in the avian retina

Citations Over TimeTop 10% of 2016 papers

Abstract

Müller glia are capable of de-differentiating and proliferating to become Müller glia-derived progenitor cells (MGPCs) with the ability to regenerate retinal neurons. One of the cell-signaling pathways that drives the reprogramming of Müller glia into MGPCs in the zebrafish retina is the Jak/Stat-pathway. However, nothing is known about the influence of Jak/Stat-signaling during the formation of MGPCs in the retinas of warm-blooded vertebrates. Accordingly, we examined whether Jak/Stat-signaling influences the formation of MGPCs and differentiation of progeny in the avian retina. We found that Jak/Stat-signaling is activated in Müller glia in response to NMDA-induced retinal damage or by CNTF or FGF2 in the absence of retinal damage. Inhibition of gp130, Jak2, or Stat3 suppressed the formation of proliferating MGPCs in NMDA-damaged and FGF2-treated retinas. Additionally, CNTF combined with FGF2 enhanced the formation of proliferating MGPCs in the absence of retinal damage. In contrast to the zebrafish model, where activation of gp130/Jak/Stat is sufficient to drive neural regeneration from MGPCs, signaling through gp130 inhibits the neurogenic potential of MGPCs and promotes glial differentiation. We conclude that gp130/Jak/Stat-signaling plays an important role in the network of pathways that drives the formation of proliferating MGPCs; however, this pathway inhibits the neural differentiation of the progeny.

Related Papers

• → Retina regeneration in zebrafish(2016)260 cited
• → Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina(2017)193 cited
• → Inflammation Regulates the Multi-Step Process of Retinal Regeneration in Zebrafish(2021)47 cited
• → Retinal regeneration in adult zebrafish requires regulation of TGFβ signaling(2013)104 cited
• → WSV181 inhibits JAK/STAT signaling and promotes viral replication in Drosophila(2018)12 cited