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Ko Park, Joseph A Brzezinski, Tatiana Eliseeva, Kenneth Jones; Identification of early retinal bipolar cell-specific genes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):717.
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© ARVO (1962-2015); The Authors (2016-present)
The mechanisms that control bipolar cell formation during retinogenesis are incompletely understood. Mice that lack the transcription factor Blimp1 (Prdm1) form bipolar cells at the expense of photoreceptors shortly after birth. To discover early bipolar cell regulators, we identified genes that were precociously upregulated in Blimp1 mutant retinas.
Postnatal day (P) 2 retinas from five Blimp1 conditional null mice and five controls were processed for high throughput RNA-sequencing. Samples were sequenced to an average depth of 30 million reads. The reads were mapped to annotated transcripts and normalized as reads per kilobase exon per million mapped reads. Genes that were statistically different between conditions and that changed at least 40% were considered candidate regulators. Candidates were further evaluated by in situ hybridization and immunohistochemistry.
RNA-seq comparison between P2 Blimp1 conditional null and control retinas revealed approximately 84 significantly upregulated genes. This included several known bipolar-specific genes, such as Vsx1 and Scgn; which we validated by immunohistochemistry. We also characterized the expression of a novel upregulated gene, Tmem215, which codes for a transmembrane protein of unknown function. We first observed Tmem215 expression by in situ hybridization in the central retinas of P2 mice. Expression spread to the periphery by P5 and became more robust in adult retinas. Tmem215 expression was confined to a narrow region within the inner retina, consistent with bipolar cell localization.
We have identified several potential early bipolar-specific genes by searching for precociously upregulated genes in Blimp1 mutant retinas. The expression of one of these candidates, Tmem215, closely paralleled the spatial and temporal pattern of bipolar cell genesis and maturation. It remains unclear what role Tmem215 plays in bipolar cell development.
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