Abstract
Müller glia are essential for retinal homeostasis, maintaining structural integrity, physiological function, and providing neurotrophic support. Müller glia also have an added role as stem cell-like cells in fish and frogs, but this regenerative property is lost in mammals. We previously showed that the imprinted gene Plagl1, encoding a zinc finger transcription factor, is expressed in murine Müller glia. Strikingly, a comparison to published scRNA-seq datasets revealed that Plagl1 is upregulated in the first few hours post-injury, but then rapidly downregulated. To test Plagl1 function in the perinatal retina, we examined Plagl1+/-pat null mutants, identifying defects in retinal architecture and visual signal processing at perinatal stages. Moreover, Plagl1+/-pat Müller glia become gliotic and proliferate ectopically in the postnatal retina. Birthdating and lineage tracing of these proliferating Müller glia revealed that they give rise to new Müller glia, but also some rod photoreceptors and amacrine cells. Transcriptomic and molecular profiling of perinatal Plagl1+/-pat retinas revealed similarities with other retinal degenerative models, including upregulation of pro-gliogenic and pro-proliferative pathways, including ERK, Notch and Hippo pathways. Strikingly, the Plagl1+/-pat transcriptome closely resembles the transcriptome of Müller glia early post-injury. Plagl1 is thus an essential component of the transcriptional regulatory networks that retain mammalian Müller glia in quiescence and sustain retinal homeostasis.