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S. Fuhrmann; Role of TGFbeta Signaling During Early Eye Development in Vertebrates . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3131.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Morphogenesis of the vertebrate eye occurs through inductive interactions between tissues of different origin; the diencephalic neuroepithelium, the surface ectoderm and head mesenchyme. Disruptions of these interactions can lead to congenital eye diseases such as coloboma, mircophthalmia and anophthalmia, thus, it is essential to determine the mechanisms underlying regional specification and differentiation of ocular tissues. Recently, we discovered in chick that the head mesenchyme is an essential regulator of early eye development at the optic vesicle stage. TFGb family members are good candidate factors to mediate this interaction. The purpose of this study is to determine whether head mesenchyme is critical for development of the mammalian eye and to identify the actual signal in the extraocular mesenchyme. Methods: Explants of optic vesicles from chick and mouse embryos were cultured under different conditions and analyzed for expression of eye–specific genes. TGFb signaling was inhibited in chick embryos and critical eye development genes were assayed for changes in expression. Candidate TGFb family members were analyzed for expression in the head mesenchyme at the optic vesicle stage using whole mount in situ hybridization. Results: Similar to our observation in chick, we find that the head mesenchyme in mouse is essential for development of the retinal pigmented epithelium (RPE). In vivo and in vitro experiments in chick suggest that the activin type II receptor mediates the effect of the extraocular mesenchyme. However, several TGFb family members such as activin bA and bB subunits, BMP3b, BMP4, BMP5, BMP6, BMP7, Nodal and Vg1 could be excluded as candidate signals. Currently, we are analyzing more members using a gene candidate approach. Conclusions:The head mesenchyme is a critical regulator of early eye development and its role appears to be conserved throughout vertebrates. Our oberservations suggest that TGFb signaling is required for inductive interaction between head mesenchyme and the presumptive RPE in the optic vesicle.
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