{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:54:11Z","timestamp":1791932051521,"version":"4.3.4"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,5,28]]},"abstract":"<jats:p>\n                    The ciliary body (CB) of the mammalian eye is responsible for secreting aqueous humor to maintain intraocular pressure, which is elevated in the eyes of glaucoma patients. It contains a folded two-layered epithelial structure comprising the nonpigmented inner ciliary epithelium (ICE), the pigmented outer ciliary epithelium (OCE), and the underlying stroma. Although the CB has an important function in the eye, its morphogenesis remains poorly studied. In this study, we show that conditional inactivation of the Jagged 1 (Jag1)-Notch2 signaling pathway in the developing CB abolishes its morphogenesis. Notch2 is expressed in the OCE of the CB, whereas Jag1 is expressed in the ICE. Conditional inactivation of\n                    <jats:italic>Jag1<\/jats:italic>\n                    in the ICE or\n                    <jats:italic>Notch2<\/jats:italic>\n                    in the OCE disrupts CB morphogenesis, but neither affects the specification of the CB region. Notch2 signaling in the OCE is required for promoting cell proliferation and maintaining bone morphogenetic protein (BMP) signaling, both of which have been suggested to be important for CB morphogenesis. Although Notch and BMP signaling pathways are known to cross-talk via the interaction between their downstream transcriptional factors, this study suggests that Notch2 maintains BMP signaling in the OCE possibly by repressing expression of secreted BMP inhibitors. Based on our findings, we propose that Jag1-Notch2 signaling controls CB morphogenesis at least in part by regulating cell proliferation and BMP signaling.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1218145110","type":"journal-article","created":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T00:29:36Z","timestamp":1368664176000},"page":"8966-8971","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye"],"prefix":"10.1073","volume":"110","author":[{"given":"Yi","family":"Zhou","sequence":"first","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"},{"name":"Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Tanzie","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"},{"name":"Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Rochester Medical Center, Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Duncan","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Gaudenz","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Seidel","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandy","family":"Lewis","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Moran","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T.","family":"Libby","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Rochester Medical Center, Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Kiernan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Rochester Medical Center, Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xie","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110;"},{"name":"Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,5,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0b013e32834ff23e"},{"key":"e_1_3_3_2_2","first-page":"123","article-title":"Development of the ciliary body: A brief review","volume":"105","author":"Beebe DC","year":"1986","unstructured":"DC Beebe, Development of the ciliary body: A brief review. 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