Reference - Detail
|Author||Vitorino M, Jusuf PR, Maurus D, Kimura Y, Higashijima S, Harris WA.|
|Title||Vsx2 in the zebrafish retina: restricted lineages through derepression.|
BACKGROUND:The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). It is not clear, however, which progenitors are multipotent or why they are multipotent.
RESULTS:In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2.
CONCLUSION:Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.
|MeSH||Amacrine Cells / cytology Amacrine Cells / metabolism Animals Cell Differentiation / genetics Cell Lineage / genetics DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Down-Regulation / genetics Eye Proteins / genetics Eye Proteins / metabolism* Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Gene Expression Regulation, Developmental / genetics Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Neurogenesis / genetics Neuroglia / cytology Neuroglia / metabolism Photoreceptor Cells, Vertebrate / cytology Photoreceptor Cells, Vertebrate / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism Retina / cytology Retina / embryology* Retina / metabolism* Retinal Bipolar Cells / cytology Retinal Bipolar Cells / metabolism Retinal Ganglion Cells / cytology Retinal Ganglion Cells / metabolism Retinal Horizontal Cells / cytology Retinal Horizontal Cells / metabolism Stem Cells / cytology Stem Cells / metabolism* Zebrafish / embryology* Zebrafish / metabolism* Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*|
|WOS Category||DEVELOPMENTAL BIOLOGY NEUROSCIENCES|