生物
骨形态发生蛋白2
细胞生物学
转录因子
眼睛发育
效应器
视网膜色素上皮
视网膜
内科学
内分泌学
遗传学
基因
生物化学
体外
医学
作者
Shuyi Mai,Xiaomin Zhu,Esther Yi Ching Wan,Shaohua Wu,Jesslyn Nagalin Yonathan,Jun Wang,Ying Li,Jessica Yuen Wuen,Bing Zuo,Dennis Y. Tse,Pui‐Chi Lo,Xin Wang,Kui Ming Chan,David M. Wu,Wenjun Xiong
出处
期刊:Development
[The Company of Biologists]
日期:2022-07-14
卷期号:149 (14)
被引量:2
摘要
Eye size is a key parameter of visual function, but the precise mechanisms of eye size control remain poorly understood. Here, we discovered that the lipogenic transcription factor sterol regulatory element-binding protein 2 (SREBP2) has an unanticipated function in the retinal pigment epithelium (RPE) to promote eye size in postnatal mice. SREBP2 transcriptionally represses low density lipoprotein receptor-related protein 2 (Lrp2), which has been shown to restrict eye overgrowth. Bone morphogenetic protein 2 (BMP2) is the downstream effector of Srebp2 and Lrp2, and Bmp2 is suppressed by SREBP2 transcriptionally but activated by Lrp2. During postnatal development, SREBP2 protein expression in the RPE decreases whereas that of Lrp2 and Bmp2 increases as the eye growth rate reduces. Bmp2 is the key determinant of eye size such that its level in mouse RPE inversely correlates with eye size. Notably, RPE-specific Bmp2 overexpression by adeno-associated virus effectively prevents the phenotypes caused by Lrp2 knock out. Together, our study shows that rapid postnatal eye size increase is governed by an RPE-derived signaling pathway, which consists of both positive and negative regulators of eye growth.
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