Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo

In vertebrates, the neuroepithelium of the optic vesicle is initially multipotential, co-expressing a number of transcription factors that are involved in retinal pigment epithelium (RPE) and neural retina (NR) development. Subsequently, extrinsic signals emanating from the surrounding tissues induce the separation of the optic vesicle into three domains: the optic stalk/nerve, the NR and the RPE. Here, we show that bone morphogenetic proteins (BMPs) are sufficient and essential for RPE development in vivo. Bmp4 and Bmp7 are expressed in the surface ectoderm overlying the optic vesicle, the surrounding mesenchyme and/or presumptive RPE during the initial stages of eye development. During the initial stages of chick eye development the microphthalmia-associated transcription factor (Mitf), important for RPE development, is expressed in the optic primordium that is covered by the BMP-expressing surface ectoderm. Following BMP application, the optic neuroepithelium, including the presumptive optic stalk/nerve and NR domain, develop into RPE as assessed by the expression of Otx2, Mitf, Wnt2b and the pigmented cell marker MMP115. By contrast, interfering with BMP signalling prevents RPE development in the outer layer of the optic cup and induces NR-specific gene expression (e.g. Chx10). Our results show that BMPs are sufficient and essential for RPE development during optic vesicle stages. We propose a model in which the BMP-expressing surface ectoderm initiates RPE specification by inducing Mitf expression in the underlying neuroepithelium of the optic vesicle.