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Joseph A Brzezinski, Sergio Groman-Lupa, Joseph Adewumi, Ko Park; The transcription factor Prdm16 marks a subset of retinal ganglion cells in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2247.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells (RGC) can be categorized into upwards of 22 morphologically distinct subtypes. How these identities are acquired is poorly understood, but it is likely that different combinations of transcription factors specify RGC subtypes during development. As a first step, we tested whether the transcription factor Prdm16 marks specific types of RGCs in the developing mouse retina.
We examined embryonic and mature retinas by immunohistochemistry for Prdm16 and several other cell type-specific markers. To better visualize the morphology of Prdm16+ cells, we utilized Thy1-YFP-H transgenic mice. In these mice, a small random population of RGCs expresses yellow fluorescent protein (YFP), which allows segregation of individual RGC dendritic arbors and morphological identification of subtype identity.
Our prior analysis showed that most of the sixteen Prdm family transcription factors are expressed during murine retinal development. We examined Prdm16 expression by immunohistochemistry and found that it was expressed in the ganglion cell layer starting late in embryonic development. Prdm16+ cell nuclei did not co-express the amacrine marker AP2a, but instead they expressed the RGC marker Brn3a. In mature retinas, Prdm16+ cells were arranged in an evenly spaced pattern. They accounted for 2.8% (± 0.3% S.D.) of the Brn3a+ RGCs, or roughly 2.1% of all ganglion cells. Prdm16+ cells did not co-express calretinin, melanopsin, or CART; but nearly all of the Prdm16+ cells co-expressed parvalbumin (99.1 ± 1.5% S.D.) at modest levels. This limited the Prdm16+ population to a couple possible subtypes. To date, we have imaged one Thy1-YFP+/Prdm16+ RGC. This cell had the morphology of the C1 subtype as classified by Sun and colleagues in 2002 (the G9 type described by Völgyi and colleagues in 2009).
We have identified Prdm16 as a marker of a small subset of ganglion cells. The evenly spaced arrangement of these cells, frequency, and marker profiles suggest that Prdm16 marks a single subtype of RGC. Characterization of individual ganglion cell subtypes in diseased eyes may increase our understanding of retinal pathophysiology. Future work will test whether Prdm16 is necessary or sufficient for the development of a specific ganglion cell subtype.
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