Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina

Cell Rep. 2021 Nov 16;37(7):109994. doi: 10.1016/j.celrep.2021.109994.


Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirm that NFI transcription factors selectively activate expression of genes promoting late-stage temporal identity in primary retinal progenitors and identify other transcription factors that regulate rod photoreceptor specification in postnatal retina. This study inventories cis- and trans-acting factors that control retinal development and can guide cell-based therapies aimed at replacing retinal neurons lost to disease.

Keywords: NFI; development; gene regulatory network; neurogenesis; progenitor; retina; single-cell ATAC-seq; single-cell RNA-seq; temporal patterning; transcription factor.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Cell Differentiation / genetics
  • Cell Lineage / genetics*
  • Eye Proteins / metabolism
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Gene Regulatory Networks / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice / embryology
  • NFI Transcription Factors / metabolism
  • Neurogenesis / genetics*
  • Retina / embryology*
  • Retinal Neurons / metabolism
  • Retinal Rod Photoreceptor Cells / metabolism
  • Trans-Activators / metabolism


  • Eye Proteins
  • Homeodomain Proteins
  • NFI Transcription Factors
  • Trans-Activators