title: NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors.
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.
authors.affiliation: 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.
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Matthew John
authors.initials: MJ
authors.lastname: Brooks
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Zelinger
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Karakülah
authors.affiliation: 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.
authors.forename: Norimoto
authors.initials: N
authors.lastname: Gotoh
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Boleda
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Linn
authors.initials: L
authors.lastname: Gieser
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Giuste
authors.affiliation: 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.
authors.forename: Dustin Thad
authors.initials: DT
authors.lastname: Whitaker
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Walton
authors.affiliation: Flow Cytometry Core, NEI, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Villasmil
authors.affiliation: Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jennifer Joanna
authors.initials: JJ
authors.lastname: Barb
authors.affiliation: Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Peter Jonathan
authors.initials: PJ
authors.lastname: Munson
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Koray Dogan
authors.initials: KD
authors.lastname: Kaya
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vijender
authors.initials: V
authors.lastname: Chaitankar
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cogliati
authors.affiliation: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: swaroopa@nei.nih.gov.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D003198:Computer Simulation; D019175:DNA Methylation / Q000235:genetics; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; C084884:Nrl protein, mouse; D012333:RNA, Messenger
keywords: Maf; RNA-seq; basic motif leucine zipper; gene regulation; neuronal development; next generation sequencing; organogenesis; photoreceptor differentiation; retina; transcription