論文 - 詳細
| RRC ID | 64748 |
|---|---|
| 著者 | Nadolski NJ, Balay SD, Wong CXL, Waskiewicz AJ, Hocking JC. |
| タイトル | Abnormal Cone and Rod Photoreceptor Morphogenesis in gdf6a Mutant Zebrafish. |
| ジャーナル | Invest Ophthalmol Vis Sci |
| Abstract |
Purpose:Analysis of photoreceptor morphology and gene expression in mispatterned eyes of zebrafish growth differentiation factor 6a (gdf6a) mutants. Methods:Rod and cone photoreceptors were compared between gdf6a mutant and control zebrafish from larval to late adult stages using transgenic labels, immunofluorescence, and confocal microscopy, as well as by transmission electron microscopy. To compare transcriptomes between larval gdf6a mutant and control zebrafish, RNA-Seq was performed on isolated eyes. Results:Although rod and cone photoreceptors differentiate in gdf6a mutant zebrafish, the cells display aberrant growth and morphology. The cone outer segments, the light-detecting sensory endings, are reduced in size in the mutant larvae and fail to recover to control size at subsequent stages. In contrast, rods form temporarily expanded outer segments. The inner segments, which generate the required energy and proteins for the outer segments, are shortened in both rods and cones at all stages. RNA-Seq analysis provides a set of misregulated genes associated with the observed abnormal photoreceptor morphogenesis. Conclusions:GDF6 mutations were previously identified in patients with Leber congenital amaurosis. Here, we reveal a unique photoreceptor phenotype in the gdf6a mutant zebrafish whereby rods and cones undergo abnormal maturation distinct for each cell type. Further, subsequent development shows partial recovery of cell morphology and maintenance of the photoreceptor layer. By conducting a transcriptomic analysis of the gdf6a larval eyes, we identified a collection of genes that are candidate regulators of photoreceptor size and morphology. |
| 巻・号 | 61(4) |
| ページ | 9 |
| 公開日 | 2020-4-9 |
| DOI | 10.1167/iovs.61.4.9 |
| PII | 2764741 |
| PMID | 32293666 |
| PMC | PMC7401959 |
| MeSH | Animals Fluorescent Antibody Technique Gene Expression Regulation, Developmental / genetics Growth Differentiation Factor 6 / genetics* In Situ Hybridization Larva Microscopy, Confocal Microscopy, Electron, Transmission Morphogenesis / genetics* Mutation / genetics Paraffin Embedding Real-Time Polymerase Chain Reaction Retinal Cone Photoreceptor Cells / physiology* Retinal Cone Photoreceptor Cells / ultrastructure Retinal Rod Photoreceptor Cells / physiology* Retinal Rod Photoreceptor Cells / ultrastructure Zebrafish / abnormalities* Zebrafish / genetics Zebrafish Proteins / genetics* |
| IF | 3.47 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(zfSWS1-5.5A:EGFP)kj9, Tg(zfRh1-3.7B:EGFP)kj2 |