Gsg1, Trnp1, and Tmem215 Mark Subpopulations of Bipolar Interneurons in the Mouse Retina

Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):1137-1150. doi: 10.1167/iovs.16-19767.


Purpose: How retinal bipolar cell interneurons are specified and assigned to specialized subtypes is only partially understood. In part, this is due to a lack of early pan- and subtype-specific bipolar cell markers. To discover these factors, we identified genes that were upregulated in Blimp1 (Prdm1) mutant retinas, which exhibit precocious bipolar cell development.

Methods: Postnatal day (P)2 retinas from Blimp1 conditional knock-out (CKO) mice and controls were processed for RNA sequencing. Genes that increased at least 45% and were statistically different between conditions were considered candidate bipolar-specific factors. Candidates were further evaluated by RT-PCR, in situ hybridization, and immunohistochemistry. Knock-in Tmem215-LacZ mice were used to better trace retinal expression.

Results: A comparison between Blimp1 CKO and control RNA-seq datasets revealed approximately 40 significantly upregulated genes. We characterized the expression of three genes that have no known function in the retina, Gsg1 (germ cell associated gene), Trnp1 (TMF-regulated nuclear protein), and Tmem215 (a predicted transmembrane protein). Germ cell associated gene appeared restricted to a small subset of cone bipolars while Trnp1 was seen in all ON type bipolar cells. Using Tmem215-LacZ heterozygous knock-in mice, we observed that β-galactosidase expression started early in bipolar cell development. In adults, Tmem215 was expressed by a subset of ON and OFF cone bipolar cells.

Conclusions: We have identified Gsg1, Tmem215, and Trnp1 as novel bipolar subtype-specific genes. The spatial and temporal pattern of their expression is consistent with a role in controlling bipolar subtype fate choice, differentiation, or physiology.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Cycle Proteins
  • Cell Differentiation
  • DNA-Binding Proteins
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • RNA / genetics*
  • Retinal Bipolar Cells / cytology
  • Retinal Bipolar Cells / metabolism*
  • Retinal Cone Photoreceptor Cells / cytology
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Trnp1 protein, mouse
  • RNA