ZFIN ID: ZDB-PUB-190105-1
Dual regulation of lin28a by Myc is necessary during zebrafish retina regeneration
Mitra, S., Sharma, P., Kaur, S., Khursheed, M.A., Gupta, S., Chaudhary, M., Kurup, A.J., Ramachandran, R.
Date: 2019
Source: The Journal of cell biology   218(2): 489-507 (Journal)
Registered Authors: Kurup, Akshai Janardhana
Keywords: none
MeSH Terms:
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Ependymoglial Cells/cytology
  • Ependymoglial Cells/metabolism
  • Gene Expression Regulation/physiology
  • Histone Deacetylase 1/genetics
  • Histone Deacetylase 1/metabolism
  • Proto-Oncogene Proteins c-myc/genetics
  • Proto-Oncogene Proteins c-myc/metabolism*
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism*
  • Regeneration/physiology*
  • Retina/physiology*
  • Signal Transduction/physiology*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 30606747 Full text @ J. Cell Biol.
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 ascl1a, a known activator of lin28a in MGPCs. Notably, mycb is simultaneously activated by Ascl1a and repressed by Insm1a in regenerating retina. Here, we unravel a dual role of Mycb in lin28a 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 her4.1, an effector of Delta-Notch signaling. Further, we also show the repressive role of Delta-Notch signaling on lin28a 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.