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Yuk Fai Leung, Yuqing Zhang, Yifan Yang, Caleb Trujillo, Wenxuan Zhong; The Expression Of Irx7 In The Inner Nuclear Layer Of Zebrafish Retina Is Essential For A Proper Retinal Development And Lamination. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1314.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous investigation on Smarca4, a retinal dystrophic mutant, has identified a number of genes for retinal differentiation (Leung et al 2008). Among them, irx7 is expressed in the prospective INL at 52hpf (Hensley et al 2011) when retinal lamination is being established, suggesting a potential role in this process. The purpose of this study was to define the role of irx7 in retinal development.
The expression dynamics of irx7 was investigated by in situ hybridization. Irx7 in developing embryos was knocked-down by microinjection of morpholinos (MOs). The resulting retinal phenotypes were characterized by immunostaining and in situ hybridization with various markers.
During retinal development, irx7’s expression was found to appear exclusively in the inner nuclear layer (INL) as soon as the prospective INL cells withdraw from the cell cycle and during retinal lamination. In Irx7-knockdown retinas, the formation of a proper retinal lamination was disrupted and the differentiation of INL cell types, including amacrine, horizontal, bipolar and Muller cells, was compromised. Despite irx7’s exclusive expression in the INL, photoreceptors differentiation was also compromised in Irx7-knockdown retinas. Compared with other retinal cell types, ganglion cells differentiated relatively well in these retinas, except for their dendritic projections into the inner plexiform layer (IPL). In fact, the neuronal projections of amacrine and bipolar cells into the IPL were also diminished. The expression of known TFs that can specify specific retinal cell type was also altered in Irx7-knockdown retinas.
These results indicate that cells in the INL and photoreceptor layers are preferentially affected. Retinal lamination issue in the Irx7-knockdown retinas is likely caused by the attenuation of neurite outgrowth of the cells in these layers. Thus, the irx7 gene network is a novel regulatory circuit for retinal development and lamination.
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