miR-203 regulates progenitor cell proliferation during adult zebrafish retina regeneration

Dev Biol. 2014 Aug 15;392(2):393-403. doi: 10.1016/j.ydbio.2014.05.005. Epub 2014 May 20.

Abstract

Damage of the zebrafish retina triggers a spontaneous regeneration response that is initiated by Müller Glia (MG) dedifferentiation and asymmetric cell division to produce multipotent progenitor cells. Subsequent expansion of the progenitor pool by proliferation is critical for retina regeneration. Pax6b expression in the progenitor cells is necessary for their proliferation, but exact regulation of its expression is unclear. Here, we show that miR-203 is downregulated during regeneration in proliferating progenitor cells. Elevated miR-203 levels inhibit progenitor cell expansion without affecting MG dedifferentiation or progenitor cell generation. Using GFP-reporter assays and gain and loss of function experiments in the retina, we show that miR-203 expression must be suppressed to allow pax6b expression and subsequent progenitor cell proliferation.

Keywords: Pax6b; Progenitor cell proliferation; Retina regeneration; miR-203.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation*
  • Cloning, Molecular
  • Electroporation
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Immunohistochemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microinjections
  • Morpholinos / genetics
  • Real-Time Polymerase Chain Reaction
  • Regeneration / physiology*
  • Retina / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Stem Cells / physiology*
  • Zebrafish / genetics
  • Zebrafish / physiology*

Substances

  • MicroRNAs
  • Mirn203 microRNA, zebrafish
  • Morpholinos