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Publication : The role of Zhx2 transcription factor in bipolar cell differentiation during mouse retinal development.

First Author  Kawamura Y Year  2018
Journal  Biochem Biophys Res Commun Volume  503
Issue  4 Pages  3023-3030
PubMed ID  30146259 Mgi Jnum  J:266115
Mgi Id  MGI:6214404 Doi  10.1016/j.bbrc.2018.08.088
Citation  Kawamura Y, et al. (2018) The role of Zhx2 transcription factor in bipolar cell differentiation during mouse retinal development. Biochem Biophys Res Commun 503(4):3023-3030
abstractText  We found that the Zhx2 gene (whose product is known to act as a tumor suppressor in hepatocellular carcinoma) is expressed in embryonic retinal progenitors and in developing cone bipolar cells in the postnatal retina, as well as in Muller glia in the mature retina. To examine the functions of Zhx2 protein during retinal development, we performed loss- and gain-of-function analyses using a retinal explant culture system. We introduced a plasmid encoding Zhx2 shRNA into isolated mouse retinas at E17.5, and the retinas were cultured as explants. After 3 days of culture, proliferation was slightly enhanced, leading to retinas thicker than in the control, but this phenomenon was observed only transiently. After 14 days of the culture, the thickness and gross morphology of retinas expressing sh-Zhx2 were indistinguishable from those of the control. The numbers of rod cells, amacrine cells, and Muller glia were the same in both groups. However, although the total number of bipolar cells was the same, the experimental group saw an increased population of ON bipolar cells, and decreased numbers of a subset of OFF bipolar cells. We also examined the effects of overexpression of Zhx2. Although Zhx2 acts as a tumor suppressor, its overexpression in developing retinas did not lead to any discernible difference in retinal thickness, suggesting that proliferation activity was not affected. After 14 days of explant culture, the total number of bipolar cells decreased, and subset composition was altered. Taken together, these results suggest that Zhx2 plays roles in the regulation of bipolar cell subset fate determination during retinal development.
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