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Raven Diacou, Xue Li, Ales Cvekl, Guillermo Oliver, Wei Liu; Elucidating the roles of homeodomain transcription factors Six3 and Six6 in retinal differentiation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):111.
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© ARVO (1962-2015); The Authors (2016-present)
Homeodomain transcription factors Six3 and Six6 (also known as Optx2) are largely co-expressed and play key roles in retinal development. Previously, we generated Six3 and Six6 compound mutant retinae in which Six3 was conditionally deleted in retinae using Pax6 alpha-Cre or CAGG-CREER at the time when retinal progenitors were just specified. The compound mutant retinae displayed novel retinal phenotypes that were not observed in any of the single mutant retinae. In this study, we aim to elucidate the roles of Six3 and Six6 in retinal differentiation at molecular levels.
1) To evaluate candidate targets of Six3 and Six6 through genetic rescue of the retinal phenotypes in mice; 2) To identify genome-wide targets of Six3 and Six6 in retinal differentiation through transcriptional profiling of the compound mutant retinae, single mutant retinae, and control retinae using RNA-seq experiments.
This is an ongoing project. Previously, we demonstrated that cell fate determination and laminar structure were disrupted in Six3 and Six6 compound mutant retinae. Importantly, the expression of Sox2 and Math5 was significantly down-regulated. Meanwhile, Wnt/b-catenin signaling was up-regulated. Here, our preliminary results show that forced Sox2 expression or reduction of Wnt/b-catenin signaling in compound mutant retinae partially rescues the retinal phenotypes. We found that Math5 expression was restored in the compound mutant retinae either by forced Sox2 expression or by reduction of Wnt/b-catenin signaling (n=3). Ongoing RNA-seq experiments will identify genome-wide targets of Six3 and Six6 in retinal differentiation.
Homeodomain transcription factors Six3 and Six6 play essential roles in retinal differentiation partially through maintaining Sox2 expression and suppressing Wnt/b-catenin signaling.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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