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Articles, Development/Plasticity/Repair

T-box Transcription Regulator Tbr2 Is Essential for the Formation and Maintenance of Opn4/Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion Cells

Chai-An Mao, Hongyan Li, Zhijing Zhang, Takae Kiyama, Satchidananda Panda, Samer Hattar, Christophe P. Ribelayga, Stephen L. Mills and Steven W. Wang
Journal of Neuroscience 24 September 2014, 34 (39) 13083-13095; https://doi.org/10.1523/JNEUROSCI.1027-14.2014
Chai-An Mao
3Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030,
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Hongyan Li
1Ruiz Department of Ophthalmology and Visual Science and
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Zhijing Zhang
1Ruiz Department of Ophthalmology and Visual Science and
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Takae Kiyama
1Ruiz Department of Ophthalmology and Visual Science and
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Satchidananda Panda
4Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, and
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Samer Hattar
5Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218
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Christophe P. Ribelayga
1Ruiz Department of Ophthalmology and Visual Science and
2Graduate School of Biomedical Sciences, University of Texas Medical School at Houston, Houston, Texas 77030,
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Stephen L. Mills
1Ruiz Department of Ophthalmology and Visual Science and
2Graduate School of Biomedical Sciences, University of Texas Medical School at Houston, Houston, Texas 77030,
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Steven W. Wang
1Ruiz Department of Ophthalmology and Visual Science and
2Graduate School of Biomedical Sciences, University of Texas Medical School at Houston, Houston, Texas 77030,
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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.

  • circadian
  • Eomes
  • ipRGC
  • retina development
  • RGC subtypes
  • Tbr2
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The Journal of Neuroscience: 34 (39)
Journal of Neuroscience
Vol. 34, Issue 39
24 Sep 2014
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T-box Transcription Regulator Tbr2 Is Essential for the Formation and Maintenance of Opn4/Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion Cells
Chai-An Mao, Hongyan Li, Zhijing Zhang, Takae Kiyama, Satchidananda Panda, Samer Hattar, Christophe P. Ribelayga, Stephen L. Mills, Steven W. Wang
Journal of Neuroscience 24 September 2014, 34 (39) 13083-13095; DOI: 10.1523/JNEUROSCI.1027-14.2014

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T-box Transcription Regulator Tbr2 Is Essential for the Formation and Maintenance of Opn4/Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion Cells
Chai-An Mao, Hongyan Li, Zhijing Zhang, Takae Kiyama, Satchidananda Panda, Samer Hattar, Christophe P. Ribelayga, Stephen L. Mills, Steven W. Wang
Journal of Neuroscience 24 September 2014, 34 (39) 13083-13095; DOI: 10.1523/JNEUROSCI.1027-14.2014
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Keywords

  • circadian
  • Eomes
  • ipRGC
  • retina development
  • RGC subtypes
  • Tbr2

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