Journal Article

Targeting of GFP to Newborn Rods by Nrl Promoter and Temporal Expression Profiling of Flow-Sorted Photoreceptors

Jing, Yuezhou, Glaser, Tom, Cheng, Hong, Khanna, Ritu, Brzezinski, Joseph A., Oh, Edwin C. T., Swaroop, Anand, Mears, Alan J., Zhu, Dongxiao, Filippova, Elena, Akimoto, Masayuki, Brooks, Matthew, Hero, Alfred, Linares, Jose-Luis, Zareparsi, Sepideh

2006

Overview

The Maf-family transcription factor Nrl is a key regulator of photoreceptor differentiation in mammals. Ablation of the Nrl gene in mice leads to functional cones at the expense of rods. We show that a 2.5-kb Nrl promoter segment directs the expression of enhanced GFP specifically to rod photoreceptors and the pineal gland of transgenic mice. GFP is detected shortly after terminal cell division, corresponding to the timing of rod genesis revealed by birthdating studies. In$Nrl^{-/-}$retinas, the GFP+ photoreceptors express S-opsin, consistent with the transformation of rod precursors into cones. We report the gene profiles of freshly isolated flow-sorted GFP+ photoreceptors from wild-type and$Nrl^{-/-}$retinas at five distinct developmental stages. Our results provide a framework for establishing gene regulatory networks that lead to mature functional photoreceptors from postmitotic precursors. Differentially expressed rod and cone genes are excellent candidates for retinopathies.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Animals / Animals, Newborn / Antibodies / Basic-Leucine Zipper Transcription Factors - deficiency / Basic-Leucine Zipper Transcription Factors - genetics / Basic-Leucine Zipper Transcription Factors - metabolism / Biological Sciences / Cell cycle / Cell Differentiation / Developmental stages / DNA-Binding Proteins - genetics / Endocrine system / Eye Proteins - genetics / Eye Proteins - metabolism / Gene expression / Gene Expression Profiling / Genes / Green Fluorescent Proteins - genetics / Green Fluorescent Proteins - metabolism / Humans / Mice / Mice, Knockout / Mice, Transgenic / Neurons / Neurons - cytology / Neurons - metabolism / Neurosciences / Photoreception / Photoreceptor Cells, Vertebrate - cytology / Photoreceptor Cells, Vertebrate - metabolism / Photoreceptors / Promoter Regions, Genetic / Recombinant Proteins - genetics / Recombinant Proteins - metabolism / Retina / Retina - cytology / Retina - growth & development / Retina - metabolism / Retinal Cone Photoreceptor Cells - cytology / Retinal Cone Photoreceptor Cells - growth & development / Retinal Cone Photoreceptor Cells - metabolism / Retinal Rod Photoreceptor Cells - cytology / Retinal Rod Photoreceptor Cells - growth & development / Retinal Rod Photoreceptor Cells - metabolism / Retinal rods / Rodents / Transgenic animals