Onecut1 and Onecut2 play critical roles in the development of the mouse retina

PLoS One. 2014 Oct 14;9(10):e110194. doi: 10.1371/journal.pone.0110194. eCollection 2014.

Abstract

The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual cells, especially among different classes of transcription factors. In this study, we show that two of those factors, Onecut1 and Onecut2, are expressed during mouse retinal development. Using mice that are deficient for each of these transcription factors, we further demonstrate a significant loss (∼70-80%) of horizontal cells in the absence of either of these proteins, while the other retinal cells appear at normal numbers. Microarray profiling experiments performed on knockout retinas revealed defects in horizontal cell genes as early as E14.5. Additional profiling assays showed an upregulation of several stress response genes in the adult Onecut2 knockout, suggesting that the integrity of the retina is compromised in the absence of normal numbers of horizontal cells. Interestingly, melanopsin, the gene coding for the photopigment found in photosensitive ganglion cells, was observed to be upregulated in Onecut1 deficient retinas, pointing to a possible regulatory role for Onecut1. Taken together, our data show that similar to Onecut1, Onecut2 is also necessary for the formation of normal numbers of horizontal cells in the developing retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 6 / physiology*
  • Homeodomain Proteins / physiology*
  • Mice, Knockout
  • Retina / cytology
  • Retina / growth & development*
  • Retina / metabolism
  • Retinal Horizontal Cells / physiology
  • Transcription Factors / physiology*
  • Transcriptome

Substances

  • Hepatocyte Nuclear Factor 6
  • Homeodomain Proteins
  • ONECUT2 protein, mouse
  • Onecut1 protein, mouse
  • Transcription Factors

Associated data

  • GEO/GSE57917
  • GEO/GSE57918

Grant support

This work was funded by start-up funds from Iowa State University provided to JMT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.