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Y Chen, JW McAvoy, R de Iongh; Expression Of Bmp And Activin Receptors During Lens Development . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3550.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The TGFß superfamily includes TGFß, BMPs and activins/inhibins. Previous studies showed that signaling via TGFß receptors is important for lens fiber differentiation (de Iongh et al., 2001, Development 128: 3995-4010). BMPs have also been shown to play a role in lens induction (Furuta, & Hogan, 1998, Genes Dev, 12:3764-3775.). In this study we investigated the expression and signaling potential of BMP and activin receptors during lens development. Methods: RT-PCR was used to examine the expression of receptors for activin (ActRIIA, ActRIIB, Alk1, Alk2) and BMP (BMPRII, Alk3, Alk6) in postnatal rat lenses. In situ hybridization (ISH) using cloned PCR fragments was used to examine the spatio-temporal expression patterns of the receptors during rat lens development and in transgenic mice (OVE550 and OVE591) that express a dominant-negative TßRII in the lens. Immunohistochemistry with specific phospho-Smad1 and 2 antibodies were used to localize phosphorylated Smads. Results: RT-PCR showed expression of ALK3, BMPRII, ActRIIA and ActRIIB but not Alk1, Alk2 or Alk6 in postnatal lenses. In situ hybridization showed similar expression patterns for Alk3, BMPRII and ActRIIA during lens development. At early embryonic stages (E12-14) the receptors were ubiquitously expressed in most ocular tissues. As the lens differentiates further (E16-P21) the expression patterns became increasingly restricted to the lens epithelium and to the transitional zone. Phosphorylated Smad 1 and 2 showed similar distribution patterns with nuclear localization of the Smads being strongest in the germinative and transitional zones. In transgenic lenses there was inappropriately increased expression of Alk3 in cortical and nuclear lens fibers. Conclusion: These results suggest that during lens development there is signaling by several members of the TGF ß superfamily. Up-regulation of the type I BMP receptor, Alk3, in fibers bereft of TßR signaling, is suggestive of a compensatory mechanism and further reinforces the notion that signaling by TGFß family members is required for terminal fiber differentiation.
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