T-box Transcription RegulatorTbr2Is Essential for the Formation and Maintenance of Opn4/Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion Cells
| Autor: | Steven W. Wang, Satchidananda Panda, Takae Kiyama, Zhijing Zhang, Chai An Mao, Samer Hattar, Stephen L. Mills, Hongyan Li, Christophe P. Ribelayga |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Retinal Ganglion Cells Melanopsin Opsin genetic structures biology Cell Survival Neurogenesis General Neuroscience Intrinsically photosensitive retinal ganglion cells Rod Opsins Articles eye diseases Mice T-box Rhodopsin biology.protein Animals Female sense organs T-Box Domain Proteins Transcription regulator Neuroscience Transcription factor |
| Zdroj: | The Journal of Neuroscience. 34:13083-13095 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | 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 thisin vivostudy, 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 whenTbr2is genetically ablated before RGC specification; and (3) most ipRGCs are eliminated whenTbr2is deleted in established ipRGCs. The few remaining ipRGCs display abnormal dendritic morphological features and functions. In addition, some Tbr2-expressing RGCs can activateOpn4expression 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. |
| Databáze: | OpenAIRE |
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