title: T-box transcription regulator Tbr2 is essential for the formation and maintenance of Opn4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells.
abstract: Opsin 4 (Opn4)/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play a major role in non-image-forming visual system. Although advances have been made in understanding their morphological features and functions, the molecular mechanisms that regulate their formation and survival remain unknown. Previously, we found that mouse T-box brain 2 (Tbr2) (also known as Eomes), a T-box-containing transcription factor, was expressed in a subset of newborn RGCs, suggesting that it is involved in the formation of specific RGC subtypes. In this in vivo study, we used complex mouse genetics, single-cell dye tracing, and behavioral analyses to determine whether Tbr2 regulates ipRGC formation and survival. Our results show the following: (1) Opn4 is expressed exclusively in Tbr2-positive RGCs; (2) no ipRGCs are detected when Tbr2 is genetically ablated before RGC specification; and (3) most ipRGCs are eliminated when Tbr2 is deleted in established ipRGCs. The few remaining ipRGCs display abnormal dendritic morphological features and functions. In addition, some Tbr2-expressing RGCs can activate Opn4 expression on the loss of native ipRGCs, suggesting that Tbr2-expressing RGCs may serve as a reservoir of ipRGCs to regulate the number of ipRGCs and the expression levels of Opn4.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, cmao@mdanderson.org steven.wang@uth.tmc.edu.
authors.forename: Chai-An
authors.identifier: http://orcid.org/0000-0001-5049-0472
authors.initials: CA
authors.lastname: Mao
authors.affiliation: Ruiz Department of Ophthalmology and Visual Science and.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Ruiz Department of Ophthalmology and Visual Science and.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Ruiz Department of Ophthalmology and Visual Science and.
authors.forename: Takae
authors.initials: T
authors.lastname: Kiyama
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, and.
authors.forename: Satchidananda
authors.initials: S
authors.lastname: Panda
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.
authors.forename: Samer
authors.initials: S
authors.lastname: Hattar
authors.affiliation: Ruiz Department of Ophthalmology and Visual Science and Graduate School of Biomedical Sciences, University of Texas Medical School at Houston, Houston, Texas 77030.
authors.forename: Christophe P
authors.initials: CP
authors.lastname: Ribelayga
authors.affiliation: Ruiz Department of Ophthalmology and Visual Science and Graduate School of Biomedical Sciences, University of Texas Medical School at Houston, Houston, Texas 77030.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Mills
authors.affiliation: Ruiz Department of Ophthalmology and Visual Science and Graduate School of Biomedical Sciences, University of Texas Medical School at Houston, Houston, Texas 77030, cmao@mdanderson.org steven.wang@uth.tmc.edu.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000818:Animals; D002470:Cell Survival; D005260:Female; D008297:Male; D051379:Mice; D055495:Neurogenesis; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D020825:T-Box Domain Proteins; D000099210:Melanopsin; C491198:Eomes protein, mouse
keywords: Eomes; RGC subtypes; Tbr2; circadian; ipRGC; retina development