NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors

Cell Rep. 2016 Nov 22;17(9):2460-2473. doi: 10.1016/j.celrep.2016.10.074.


Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis. Rod-specific temporal DNA methylation corroborated gene expression patterns. De novo assembly and alternative splicing analyses revealed previously unannotated rod-enriched transcripts and the role of NRL in transcript maturation. Furthermore, we defined the relationship of NRL with other transcriptional regulators and downstream cognate effectors. Our studies provide the framework for comprehensive system-level analysis of the GRN underlying the development of a single sensory neuron, the rod photoreceptor.

Keywords: Maf; RNA-seq; basic motif leucine zipper; gene regulation; neuronal development; next generation sequencing; organogenesis; photoreceptor differentiation; retina; transcription.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Animals, Newborn
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Differentiation / genetics
  • Computer Simulation
  • DNA Methylation / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Annotation
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Transcriptome / genetics*


  • Basic-Leucine Zipper Transcription Factors
  • Eye Proteins
  • Nrl protein, mouse
  • RNA, Messenger