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Yi Zhou, Brandy Lewis, Ting Xie; RBPJ-Dependent and -Independent Regulation of BMP Signaling by Notch2 during Ciliary Body Development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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© ARVO (1962-2015); The Authors (2016-present)
The ciliary body (CB) is composed of the inner ciliary epithelium (ICE) and the outer pigmented ciliary epithelium (OCE), and is responsible for the secretion of aqueous humor and lens accommodation. Our previous work shows that Notch2 signaling controls CB morphogenesis via regulation of BMP signaling and cell proliferation. Canonical Notch signaling is mediated through RBPJ-dependent gene regulation. Here, we determined the roles of RBPJ in Notch2 signaling during CB development.
We conditionally inactivate Rbpj and Notch2 in the developing CB by crossing Trp1-Cre with floxed conditional mutations. Standard histology, immunohistochemistry and mRNA in situ hybridization were used to characterize the mutant phenotypes of Rbpj mutant eyes in comparison with those of Notch2 mutant eyes.
The ablation of Rbpj in the CB leads to its morphogenesis and secretion defects. Like Notch2 mutant CBs, Rbpj mutant CBs exhibit normal cell fate specification and Col IX secretion, and decrease cell proliferation and BMP signaling in the OCE. Unlike Notch2 mutant CBs, Rbpj mutant CBs frequently separate the ICE from the OCE possibly due to decreased N-cadherin accumulation in the ICE-OCE junction, and decrease Opticin expression and secretion in the ICE. Surprisingly, Notch2, but not RBPJ, is required in the developing CB to maintain active BMP signaling in the underlying stromal cells.
This study has revealed important roles of RBPJ in regulating CB development and secretion, and has also uncovered RBPJ–independent regulation of BMP signaling by Notch2 as well as Notch2-independent RBPJ functions in the developing CB.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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