title: Jak/Stat signaling regulates the proliferation and neurogenic potential of Müller glia-derived progenitor cells in the avian retina.
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.
authors.affiliation: Department of Neuroscience, College of Medicine, The Ohio State University, 4190 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA.
authors.forename: Levi
authors.initials: L
authors.lastname: Todd
authors.affiliation: Department of Neuroscience, College of Medicine, The Ohio State University, 4190 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Squires
authors.affiliation: Department of Neuroscience, College of Medicine, The Ohio State University, 4190 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA.
authors.forename: Lilianna
authors.initials: L
authors.lastname: Suarez
authors.affiliation: Department of Neuroscience, College of Medicine, The Ohio State University, 4190 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA.
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Fischer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002645:Chickens; D053612:Janus Kinases / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology*; D012038:Regeneration; D012160:Retina / Q000166:cytology* / Q000293:injuries; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases