title: Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye.
abstract: 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 Jag1 in the ICE or Notch2 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.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Christopher
authors.initials: C
authors.lastname: Tanzie
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Yan
authors.forename: Shuyi
authors.initials: S
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Duncan
authors.forename: Karin
authors.initials: K
authors.lastname: Gaudenz
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Christopher
authors.initials: C
authors.lastname: Seidel
authors.forename: Brandy
authors.initials: B
authors.lastname: Lewis
authors.forename: Andrea
authors.initials: A
authors.lastname: Moran
authors.forename: Richard T
authors.initials: RT
authors.lastname: Libby
authors.forename: Amy E
authors.initials: AE
authors.lastname: Kiernan
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D049109:Cell Proliferation; D002924:Ciliary Body / Q000254:growth & development*; D017931:DNA Primers / Q000235:genetics; D004848:Epithelium / Q000254:growth & development*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051379:Mice; D046228:Microarray Analysis; D009024:Morphogenesis / Q000502:physiology*; D051883:Receptor, Notch2 / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497765:Notch2 protein, mouse; D051883:Receptor, Notch2; D000072099:Serrate-Jagged Proteins