Linking YAP to Müller glia quiescence exit in the degenerative retina
Contrasting with fish or amphibian, retinal regeneration from Muller glial cells is largely limited in mammals. In our quest towards the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP, which we previously found to be upregulated in Muller cells following retinal injury. We report that conditional Yap deletion in Muller cells prevents the upregulation of cell cycle genes that normally accompanies reactive gliosis upon photoreceptor cell death. This occurs as a consequence of defective EGFR signaling. Consistent with a function of YAP in triggering Muller glia cell cycle re-entry, we further show that in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. Finally, and noteworthy, we reveal that YAP overactivation in mouse Muller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Muller cell response to injury and highlight a novel YAP-EGFR axis by which Muller cells exit their quiescence state, a critical step towards regeneration.