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Mei Xin, masahide sakabe, Yoshi Odaka, Marcus Fruttiger, Qing Lu, Richard A Lang; Hippo signaling effector Yap regulates hyaloid vasculature regression in the developing eye. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5306. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular remodeling is essential for normal organ development and function. Hyaloid vessels are important for nourishing the lens during embryonic eye development, and after birth, regression of the vessels is required for clearing the optical path. Defects in hyaloid regression leads to eye diseases such as Persistent Fetal Vasculature (PFV). The molecular mechanisms underlying hyaloid vessel regression are not fully understood. Here, we have identified that the Hippo signaling pathway regulates the regression of hyaloid vessels.
We used genetic gain-of-function and loss-of-function mouse models to dissect important roles the Hippo pathway in hyaloid regression.
We found that the cellular translocation of Yes associated protein (Yap), a Hippo signaling effector, is crucial for the regression process. Yap translocates from the nucleus to the cytoplasm when the hyaloid vessels start to regress. Retention of nuclear Yap caused by endothelial-specific deletion of the two upstream inhibitory kinases Lats1 and Lats2, or by overexpression of a constitutively-active form of Yap (YapS112A) results in persistent hyaloid vessels. Moreover, overexpression of YapS112A inhibits apoptosis without affecting endothelial cell proliferation. VEGF-A in the vitreous cavity is significantly increased in YapS112A transgenic mice, suggesting that Yap maintains the hyaloid structure in the developing eye.
Our results suggest that the Hippo signaling pathway modulates hyaloid vessel regression by promoting cell survival and maintaining VEGF-A expression during eye development.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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