Understanding the molecular mechanisms of Mycs and Hdacs to control Her 4 1 Lin 28 a let 7 regulatory axis during zebrafish retina regeneration

Abstract

Vision loss due to retinal damage, to date, proves to be a major health problem. In mammals, newlineretina, being a part of the Central Nervous System (CNS), does not possess the ability to newlineregenerate after an insult. Surprisingly, other vertebrates such as teleosts or urodeles possess newlineremarkable regenerative potential in various tissues or organs. Zebrafish, being one of the most newlineextensively studied teleosts, serves as a great model organism to study regeneration of retina. newlineBesides, being one of the most easily accessible parts of the CNS, retina serves as an ideal newlinemodel system for studying the detailed molecular mechanisms underlying a successful retinal newlineregeneration. Following an injury, Muller Glia (MG) cells, the only type of glial cells, present newlinein the retina, de-differentiate to form Muller glial derived progenitor cells (MGPCs) with stem newlinecell-like properties which further proliferate and differentiate to all retinal cell types across newlineevery retinal layer, including MG itself, to compensate for the damage. Till now, a plethora of newlinegenetic factors including transcriptional activators (e.g. Ascl1a), transcriptional repressors (e.g. newlineInsm1a, Her4.1), pluripotency-inducing factors (e.g. Lin28a), growth factors (e.g. Hb-egf), newlinecytokines (e.g. interleukins), and epigenetic modifiers (e.g. Dnmts) have been identified to play newlinesignificant roles regulating the cellular process of retina regeneration. In spite of accumulation newlineof this vast knowledge about the molecular regulators of retina regeneration in zebrafish, newlinetherapeutic interventions towards successful mammalian retinal regeneration still remains an newlineunsolved enigma in mammals, demanding further investigation. In this study, we report rapid newlineand MGPCs-associated induction of zebrafish Myc genes, namely myca and mycb which are newlinenecessary for a successful retinal repair. We also show the stringent regulation of mycb by newlinepreviously characterized Ascl1a/Insm1a regulatory axis. Further, our study places Mycb, newlinewhich is a de facto transcriptional activator, as a dual regulator acti