Retinal development anomalies and cone photoreceptors degeneration upon Bmi1 deficiency

• DOI: 10.1242/dev.125351
• Publication Date: 2016-03-11T03:15:02Z
• Authors: Andrea Barabino; Vicky Plamondon; Mohamed Abdouh; Wassim Chatoo; Anthony Flamier; Roy Hanna; Shufeng Zhou; Noboru Motoyama; Marc Hébert; Joëlle Lavoie; Gilbert Bernier
• Keywords: BMI1; Photoreceptor Degeneration; Macular Degeneration; Optogenetics; Visual phototransduction

Retinal development occurs through the sequential but overlapping generation of six neuronal and one glial cell types. Of these, rod cone photoreceptors represent functional unit light detection phototransduction are frequently affected in retinal degenerative diseases. During mouse development, Polycomb group protein Bmi1 is expressed immature progenitors differentiated neurons, including cones. We show here that required to prevent post-natal degeneration bipolar inactivation Chk2 or p53 could improve not overcome Bmi1−/− mice. The phenotype mice was also characterized by loss heterochromatin, activation tandem-repeats, oxidative stress, Rip3-associated necroptosis. In human retina, BMI1 preferentially cones at heterochromatic foci. embryonic stem cells compatible with induction impaired terminal differentiation. Despite this developmental arrest, BMI1-deficient recapitulated several anomalies observed such as tandem-repeats induction, revealing partly conserved biological functions between man.