Nuclear hormone receptors play a major role in the development of many tissues. This study uncovers a novel role for testicular receptor 2 (Tr2, Nr2c1) in defining the early phase of retinal development and regulating normal retinal cell patterning and topography. The mammalian retina undergoes an overlapping yet biphasic period of development to generate all seven retinal cell types. We discovered that Nr2c1 expression coincides with development of the early retinal cells. Loss of Nr2c1 causes a severe vision deficit and impacts early, but not late retina cell types. Retinal cone cell topography is disrupted with an increase in displaced amacrine cells. Additionally, genetic background significantly impacts phenotypic outcome of cone photoreceptor cells but not amacrine cells. Chromatin-IP experiments reveal NR2C1 regulates early cell transcription factors that regulate retinal progenitor cells during development, including amacrine (Satb2) and cone photoreceptor regulators thyroid and retinoic acid receptors. This study supports a role for Nr2c1 in defining the biphasic period of retinal development and specifically influencing the early phase of retinal cell fate.
[1]Schepens Eye Res Inst Massachusetts Eye & Ear, Boston, MA 02114 USA.
[2]Harvard Med Sch, Dept Ophthalmol, Boston, MA USA.
[3]Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Ophthalmol & Visual Sci, Shanghai, Peoples R China.
[4]Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE USA.
[5]Univ Bern, Bern Univ Hosp, Dept Ophthalmol, Bern, Switzerland.
[6]Moran Eye Ctr Translat Med, Salt Lake City, UT USA.
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