TY - JOUR T1 - <em>Yap</em> haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy JF - bioRxiv DO - 10.1101/2020.02.18.953943 SP - 2020.02.18.953943 AU - Christel Masson AU - Diana García-García AU - Juliette Bitard AU - Élodie-Kim Grellier AU - Jérôme E. Roger AU - Muriel Perron Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/02/19/2020.02.18.953943.abstract N2 - Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene compensation. At post-natal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterized by EGFR signalling potentiation and delayed cell cycle exit of retinal progenitors. In contrast, Yap+/- adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Müller glia dysfunction, late-onset cone degeneration and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Müller cell specific conditional Yap knockout mice. Together, this study highlights a novel YAP function in Müller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human. This study finds unsuspected dynamics of YAP compensatory mechanisms in the retina of Yap+/- miceYap haploinsufficiency results in Müller glia dysfunction in aged mice, leading to late-onset cone dystrophy ER -