Format

Send to

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

NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors.

Author information

1
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA; Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea.
2
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
3
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
4
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA.
5
Flow Cytometry Core, NEI, National Institutes of Health, Bethesda, MD 20892, USA.
6
Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892, USA.
7
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: swaroopa@nei.nih.gov.

Abstract

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

PMID:
27880916
PMCID:
PMC5131731
DOI:
10.1016/j.celrep.2016.10.074
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center