Reciprocal actions of microRNA-9 and TLX in the proliferation and differentiation of retinal progenitor cells

Stem Cells Dev. 2014 Nov 15;23(22):2771-81. doi: 10.1089/scd.2014.0021. Epub 2014 Jul 14.


Recent research has demonstrated critical roles of a number of microRNAs (miRNAs) in stem cell proliferation and differentiation. miRNA-9 (miR-9) is a brain-enriched miRNA. Whether miR-9 has a role in retinal progenitor cell (RPC) proliferation and differentiation remains unknown. In this study, we show that miR-9 plays an important role in RPC fate determination. The expression of miR-9 was inversely correlated with that of the nuclear receptor TLX, which is an essential regulator of neural stem cell self-renewal. Overexpression of miR-9 downregulated the TLX levels in RPCs, leading to reduced RPC proliferation and increased neuronal and glial differentiation, and the effect of miR-9 overexpression on RPC proliferation and differentiation was inhibited by the TLX overexpression; knockdown of miR-9 resulted in increased TLX expression as well as enhanced proliferation of RPCs. Furthermore, inhibition of endogenous TLX by small interfering RNA suppressed RPC proliferation and promoted RPCs to differentiate into retinal neuronal and glial cells. These results suggest that miR-9 and TLX form a feedback regulatory loop to coordinate the proliferation and differentiation of retinal progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Neural Stem Cells / physiology
  • RNA, Small Interfering / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Retina / physiology*
  • Stem Cells / physiology*


  • MIRN9 microRNA, mouse
  • MicroRNAs
  • Nr2e1 protein, mouse
  • RNA, Small Interfering
  • Receptors, Cytoplasmic and Nuclear