PT  - JOURNAL ARTICLE
AU  - Annaïg Hamon
AU  - Divya Ail
AU  - Diana García-García
AU  - Juliette Bitard
AU  - Deniz Dalkara
AU  - Morgane Locker
AU  - Jérôme Roger
AU  - Muriel Perron
TI  - Linking YAP to Müller glia quiescence exit in the degenerative retina
AID  - 10.1101/431254
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 431254
4099  - http://biorxiv.org/content/early/2018/09/30/431254.short
4100  - http://biorxiv.org/content/early/2018/09/30/431254.full
AB  - Contrasting with fish or amphibian, retinal regeneration from Müller 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 Müller cells following retinal injury. We report that conditional Yap deletion in Müller 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 Müller 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 Müller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell response to injury and highlight a novel YAP-EGFR axis by which Müller cells exit their quiescence state, a critical step towards regeneration.