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Joerg Steinfeld, Ichie Ushijima, Paul G. Layer, Masasuke Araki, Astrid Vogel-Hoepker; Wnt Mediated Signaling From Surface Ectoderm Is Involved In RPE Specification During Chick Eye Development. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3947.
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© ARVO (1962-2015); The Authors (2016-present)
The vertebrate eye forms through evagination of the optic vesicle from the neuroepithelium of the prosencephalon. Extrinsic signals released from surrounding tissues are involved in patterning the optic vesicle into a NR and RPE domain. The current model of optic vesicle patterning assumes, that distally Fibroblast Growth Factors (FGFs) released from the overlying surface ectoderm are involved in NR specification, while proximally signals released from the ocular mesenchyme are involved in RPE specification. However, our previous studies suggested, that the chick optic vesicle is initially patterned into a ventral NR and dorsal RPE domain. Bone morphogenetic proteins (BMPs) and FGFs are expressed in the surface ectoderm and are involved in RPE and NR specification respectively. These signals are initially expressed throughout the surface ectoderm, suggesting that another signal might be involved in patterning the optic vesicle initially into a dorsal RPE and ventral NR domain. Wnt signaling is required for dorsal patterning of the neural tube, brain and limb. We therefore asked, whether WNTs might be involved in patterning the dorsal optic vesicle and hence RPE development.
Gain- and Loss-of-function studies were carried out by implanting protein soaked beads into the chick optic vesicle at stages 8 to 11. Effects were analysed on a molecular level by immunohistochemistry using Mitf-Antibodies and in situ hybridization for marker genes that distinguish the RPE and NR.
During optic vesicle stages WNT-family members are expressed in the dorsal ectoderm and in the presumptive RPE. Implantation of Wnt3a-soaked beads into the optic vesicle converts the entire neuroepithelium of the optic vesicle, including the presumptive optic stalk and neural retina region, into a single-layered and strongly pigmented RPE. Moreover, these cells express the two key transcription factors involved in RPE specification and differentiation, Mitf and Otx2. In contrast, NR-specific genes are downregulated following WNT exposure. On the other hand, interferring with WNT signaling results in the downregulation of Mitf expression.
We propose a new model, where the optic vesicle is initially patterned into a dorsal RPE domain by both BMP and WNT signals released from the overlying ectoderm, while ventrally BMPs and FGFs are involved in NR specification.
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