title: Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells.
abstract: During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death.
  
  
  
  Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several differentially expressed genes were assessed by quantitative RT-PCR (RT-qPCR). Protein expression level and retinal cellular localization were determined by western blot and immunohistochemistry, respectively.
  
  
  
  Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss.
  
  
  
  This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathologic conditions.
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris-Sud, Université Paris-Saclay, Orsay, France 2Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France.
authors.forename: Annaïg
authors.initials: A
authors.lastname: Hamon
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris-Sud, Université Paris-Saclay, Orsay, France 2Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Masson
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris-Sud, Université Paris-Saclay, Orsay, France 2Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Bitard
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Linn
authors.initials: L
authors.lastname: Gieser
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris-Sud, Université Paris-Saclay, Orsay, France 2Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France.
authors.forename: Jérôme E
authors.initials: JE
authors.lastname: Roger
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris-Sud, Université Paris-Saclay, Orsay, France 2Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Perron
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse