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Scott J Neal, Qingxiang Zhou, Dana F DeSantis, Francesca Pignoni; Yki (YAP-TAZ) promotes non-neural PE fate and is regulated by the PP2A phosphatase. Invest. Ophthalmol. Vis. Sci. 2017;58(8):104.
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© ARVO (1962-2015); The Authors (2016-present)
In the developing Drosophila eye (eye disc), the peripodial epithelium (PE) is developmentally analogous to the Retinal Pigmented Epithelium (RPE) of the vertebrate optic vesicle. In both, the Yorkie/Yki (YAP and TAZ in vertebrates) transcriptional cofactor promotes the non-neural fate, PE or RPE. Here we investigate the molecular mechanism(s) by which Yki controls this fate choice.
RNAi and a novel conditional loss-of function (cLOF) approach were used to impair gene function. Mutants: ykiB5, Ckas1883, and Cka05836; RNAi transgenes: UAS-ykiRNAi, UAS-hpoRNAi, UAS-CkaRNAi; UAS-StripRNAi; UAS-twsRNAi; UAS-PP2A-B’RNAi; UAS-wdbRNAi; overexpression transgenes: UAS-Hpo, UAS-DIAP1, UAS-CycE. cLOF was induced via ey-FLP, whereas UAS expression was driven by the eye-disc specific constitutive ey-FLP act>interruption cassette>GAL4 driver. Tissue was assessed by IHC and confocal microscopy for retinal, neuronal, PE markers and DAPI; incompletely penetrant phenotypes where statistically analyzed.
We investigated the roles of factors that execute or regulate Yki function. As Yki is known to promote cell proliferation and survival in Metazoa, we probed whether these functions of Yki are concomitant or distinct from its role in cell fate. We found that exogenous expression of the cell death inhibitor DIAP1 and the cell cycle regulator CycE (known targets of Yki) rescued cell survival and proliferation in yki LOF eye discs. Neither alone, nor the two together, rescued PE fate, thus showing this to be a distinct function of Yki, through other effectors. We also identified the STRIPAK-PP2A phosphatase complex as a Yki-dependent promoter of PE fate. LOF of STRIPAK-PP2A components induced a PE-to-Retina transformation that is suppressed by Hpo LOF. Since Hpo is a negative regulator of Yki that induces a PE-to-Retina transformation when overexpressed, STRIPAK-PP2A likely promotes Yki activity and PE fate through the negative regulation of the Hpo kinase.
In the Drosophila eye disc, as in the vertebrate optic vesicle, the binary choice between the neural retina and its support tissue is dependent on Yki. Yki function in PE fate is independent of its role in proliferation and cell survival. In addition, STRIPAK-PP2A is a positive regulator of Yki function, upstream of Hpo. Given the conservation of Yki and YAP-TAZ functions in the eye, these mechanisms are likely also at work in the RPE.
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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