Purchase this article with an account.
DC Beebe, TL Belecky-Adams, R Adler; Signaling Through BMP and Activin Receptors Regulates Lens Fiber Cell Differentiation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3882.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify the signaling pathways involved in lens fiber cell differentiation. Methods: We assessed the contribution of BMPs and activins to the differentiation of lens fiber cells by measuring cell elongation in chicken embryo lens epithelial explants in the presence or absence of noggin and/or follistatin. Noggin and follistatin inhibit BMP and activin signaling, respectively. Antibodies to phosphorylated SMAD1 (pSMAD1; BMP pathway) and pSMAD2 (activin pathway) were used to identify the lens cells in which the respective signaling pathways were active in vivo. Antibody staining was evaluated by confocal microscopy. Growth factor expression was detected by in situ hybridization. Results: We previously reported that over expression of noggin in vivo or addition of noggin to vitreous humor in vitro reduced, but did not prevent, lens fiber cell elongation. These results indicated that BMP signaling contributes to fiber cell differentiation. Consistent with this conclusion, we found that the nuclei of elongating fiber cells stained for pSMAD1. We now report that fiber cells stain for nuclear pSMAD2, suggesting that the activin/TGFß signaling pathway is also active during fiber cell differentiation. Nuclear pSMAD1 was most abundant during the initial stages of fiber cell elongation, while pSMAD2 was present in the nuclei of all fiber cells. E6 lens epithelial cells elongate when treated with chicken or bovine vitreous humor. Elongation was reduced when epithelial cells were treated with vitreous humor plus noggin and completely blocked by addition of both noggin and follistatin. Follistatin alone did not inhibit fiber cell elongation. In preliminary experiments, BMPs or activin alone did not promote cell elongation, but BMPs and activin together stimulated elongation to the same extent as vitreous humor. BMP and activin mRNAs were expressed in the eye throughout development. Conclusion: Members of the BMP and activin families plays key roles in lens fiber cell differentiation.
This PDF is available to Subscribers Only