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Jhenya Nahreini, Tatiana Eliseeva, Ana Uruena, Jane E. Johnson, Joseph A Brzezinski; Prdm13 does not specify amacrine or horizontal cell fates in the developing mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2240.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple genes, such as the transcription factor Ptf1a, are important for the formation of amacrine and horizontal cells during retinal development. Prior work has shown that the transcription factor Prdm13 is a downstream target of Ptf1a in the retina and spinal cord. In this study, we determined the Prdm13 expression domain throughout development, and tested whether mice that lack this transcription factor have defects in amacrine and horizontal interneuron formation.<br />
We examined mouse retinas at multiple developmental stages with antibodies against Prdm13 and other cell type-specific markers. A Prdm13-GFP knock-in allele was made to track the expression of this gene while simultaneously removing its function. <br />
Using antibodies against Prdm13, we observed most Ptf1a+ cells co-expressed Prdm13 during development. At early times, Prdm13+ cells were an obligate subset of the Ptf1a+ population. As development proceeded, Prdm13 was expressed by a medium-sized subset of amacrine cells. Using heterozygous knock-in mice, we determined that Prdm13-GFP+ amacrine cells are a complex population: 53% expressed GLYT1, 8% made GAD67, 27% made calretinin, 22% made AP2a, and none expressed calbindin or Sox2. At E17.5, Prdm13-GFP homozygous knock-out mice had a grossly normal retina. These mutants did not lack horizontal or amacrine cells at this stage, nor did the number of ganglion cells increase. Interestingly, both GFP+ and Ptf1a+ cells were more likely to co-express Otx2 in mutants.
Prdm13 is expressed in developing amacrine and horizontal cells and marks multiple subtypes of adult amacrine cells. Amacrines and horizontals are present in E17.5 mutant mice, indicating that Prdm13 is not required for the specification of either cell fate. However, the increase in Otx2 expression in mutants suggests that some amacrines and horizontals may lose their identity in favor of photoreceptor or bipolar fates later in development. Since Prdm13 knock-out mice die around birth, we plan to investigate the status of amacrine and horizontal cells in retinal explant cultures.<br />
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