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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.<\/jats:p>","DOI":"10.1242\/dev.200633","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T04:42:25Z","timestamp":1657773745000},"source":"Crossref","is-referenced-by-count":17,"title":["Postnatal eye size in mice is controlled by SREBP2-mediated transcriptional repression of <i>Lrp2<\/i> and <i>Bmp2<\/i>"],"prefix":"10.1242","volume":"149","author":[{"given":"Shuyi","family":"Mai","sequence":"first","affiliation":[{"name":"City University of Hong Kong 1 Department of Biomedical Sciences , , Hong Kong , China"},{"name":"Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong 2 Key Laboratory of Biochip Technology , , Shenzhen , China"},{"name":"Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences 3 , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"City University of Hong Kong 1 Department of Biomedical Sciences , , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Yi Ching","family":"Wan","sequence":"additional","affiliation":[{"name":"City University of Hong Kong 1 Department of Biomedical Sciences , , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyu","family":"Wu","sequence":"additional","affiliation":[{"name":"City University of Hong Kong 1 Department of Biomedical Sciences , , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesslyn Nagalin","family":"Yonathan","sequence":"additional","affiliation":[{"name":"City University of Hong Kong 1 Department of Biomedical Sciences , , Hong Kong , 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