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Y. Ouchi, M.M. Taketo, S. Watanabe; ß–Catenin Signaling Regulates Maturation of Mouse Retinal Progenitor Cells by Preventing Premature Differentiation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5758.
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© ARVO (1962-2015); The Authors (2016-present)
Wnt signal is a key factor that controls stem cells expansion in many tissues. In the retina, several studies using lower vertebrates show that Wnt signal plays important roles in the maintenance and proliferation of CMZ retinal progenitor cells. Although specific Wnt members are expressed in a peripheral region of mammalian retina, it remains unknown whether this region is enriched in immature progenitor cells. In addition, roles of Wnt signaling in early retinal development are not clarified in mammals. In this study, we investigate the Wnt–ß–catenin signalling pathway regarding proliferation and differentiation of retinal progenitor cells (RPCs).
Using a retrovirus vector, we expressed various mutants of Wnt signal members, such as constitutively active (ca) forms of ß–catenin and LEF, and dominant–negative (dn) form of LEF, in E17.5 mouse retinal explant cultures. Proliferation, differentiation and cell morphology of virus–infected cells were analyzed. Molecular mechanisms were analyzed using PC12 cells. For in vivo studies, genetically engineered mice were used to activate or inactivate ß–catenin signals in a tissue specific manner.
The results with retinal explants and PC12 cells suggested: 1) Activation of ß–catenin–Lef1 inhibits neurite outgrowth of both retinal and PC12 cells. 2) Conversely, neurite outgrowth was enhanced in cells expressing dominant–negative Lef–1. 3) Proliferation and differentiation remained unaffected in these cells. The retina–specific activation of ß–catenin in mice suggested: 1) Expansion of the immature progenitor cell region in embryonic mice. 2) Proliferating RPCs remained in retina derived from 7–week–old mice.
We found that the ß–catenin signaling controls retinal development in mice by regulating the timing of retinal progenitor cell maturation.
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