Dual regulation of by Myc is necessary during zebrafish retina regeneration.

Cellular reprogramming leading to induction of Muller glia-derived progenitor cells (MGPCs) with stem cell characteristics is essential for zebrafish retina regeneration. Although several regeneration-specific genes are characterized, the significance of MGPC-associated Mycb induction remains unknown. Here, we show that early expression of Mycb induces expression of genes like , a known activator of in MGPCs. Notably, is simultaneously activated by Ascl1a and repressed by Insm1a in regenerating retina. Here, we unravel a dual role of Mycb in expression, both as an activator through Ascl1a in MGPCs and a repressor in combination with Hdac1 in neighboring cells. Myc inhibition reduces the number of MGPCs and abolishes normal regeneration. Myc in collaboration with Hdac1 inhibits , an effector of Delta-Notch signaling. Further, we also show the repressive role of Delta-Notch signaling on expression in post-injured retina. Our studies reveal mechanistic understanding of Myc pathway during zebrafish retina regeneration, which could pave way for therapeutic intervention during mammalian retina regeneration.