Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France
Juliette Bitard
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France; Centre d′Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France
Karine Parain
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Institute of Developmental Biochemistry, University of Goettingen, Goettingen, Germany
Romain Chemouny
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France
Christel Masson
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France; Centre d′Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France
Caroline Borday
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France
Marie Hedderich
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Institute of Developmental Biochemistry, University of Goettingen, Goettingen, Germany
Kristine A Henningfeld
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Institute of Developmental Biochemistry, University of Goettingen, Goettingen, Germany
Morgane Locker
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France
Odile Bronchain
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France
Muriel Perron
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Orsay, France; Centre d′Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, France; Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, United States
The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability.
