Samd7 represses short-wavelength cone genes to preserve long-wavelength cone and rod photoreceptor identity

Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2402121121. doi: 10.1073/pnas.2402121121. Epub 2024 Nov 12.

Abstract

The role of transcription factors in photoreceptor gene regulation is fairly well understood, but knowledge of the cell-type-specific function of transcriptional cofactors remains incomplete. Here, we show that the transcriptional corepressor samd7 promotes rod differentiation and represses short-wavelength cone genes in long-wavelength cones in zebrafish. In samd7-/- retinas, red cones are transformed into hybrid red/ultraviolet (UV) cones, green cones are absent, the number of blue cones is approximately doubled, and the number of rods is greatly reduced. We also find that mouse Samd7 represses S-opsin expression in dorsal M-cones-analogous to its role in repressing UV cone genes in zebrafish red cones. Thus, samd7 plays a key role in ensuring appropriate patterns of gene expression in rods and cone subtypes of both zebrafish and mice.

Keywords: development; photoreceptor; retina.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Gene Expression Regulation
  • Mice
  • Mice, Knockout
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retinal Cone Photoreceptor Cells* / metabolism
  • Retinal Rod Photoreceptor Cells* / metabolism
  • Zebrafish Proteins* / genetics
  • Zebrafish Proteins* / metabolism
  • Zebrafish* / genetics

Substances

  • Zebrafish Proteins
  • Repressor Proteins