Contrasting with fish or amphibian, retinal regeneration from Mller 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 Mller cells following retinal injury. We report that conditional Yap deletion in Mller 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 Mller 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 Mller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Mller cell response to injury and highlight a novel YAP-EGFR axis by which Mller cells exit their quiescence state, a critical step towards regeneration. SOURCE: Jerome,Eric,Roger (jeromeeroger@gmail.com) - Neuro-PSI CNRS-Universite Paris Sud

Pluto Bioinformatics

GSE121858: Linking YAP to Mller glia quiescence exit in the degenerative retina