Linking YAP to Müller Glia Quiescence Exit in the Degenerative Retina

Cell Rep. 2019 May 7;27(6):1712-1725.e6. doi: 10.1016/j.celrep.2019.04.045.


Contrasting with fish or amphibian, retinal regeneration from Müller glia is largely limited in mammals. In our quest toward the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP (Yes-associated protein), which is upregulated in Müller cells following retinal injury. Conditional Yap deletion in mouse Müller cells prevents cell-cycle gene upregulation that normally accompanies reactive gliosis upon photoreceptor cell death. We further show that, in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. In the mouse retina, where Müller cells do not spontaneously proliferate, YAP overactivation is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell proliferative response to injury and highlight a YAP-EGFR (epidermal growth factor receptor) axis by which Müller cells exit their quiescence state, a critical step toward regeneration.

Keywords: EGFR pathway; Hippo/YAP pathway; Müller cells; reactive gliosis; retinal regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle* / genetics
  • Cell Proliferation
  • Ependymoglial Cells / metabolism
  • Ependymoglial Cells / pathology*
  • Epidermal Growth Factor / metabolism
  • Humans
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuroglia / metabolism
  • Neuroglia / pathology*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology
  • Retina / metabolism
  • Retina / pathology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology*
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Transcription, Genetic
  • Up-Regulation / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis
  • YAP-Signaling Proteins


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Trans-Activators
  • Xenopus Proteins
  • YAP protein, Xenopus
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Epidermal Growth Factor