Cloning and characterization of a secreted frizzled-related protein that is expressed by the retinal pigment epithelium

The Wnt/frizzled cell signaling pathway has been implicated in the determin ation of polarity in a number of systems, including the Drosophila retina,T he vertebrate retina develops from an undifferentiated neuroepithelium into an organized and laminated structure that demonstrates a high degree of po larity at both the tissue and cellular levels. In the process of searching for molecules that are preferentially expressed by the vertebrate retinal p igment epithelium (RPE), we identified secreted frizzled-related protein 5 (SFRP5), a member of the SFRP family that appears to act by modulating Wnt signal transduction, SFRP5 is highly expressed by RPE cells, and is also ex pressed in the pancreas, Within the retina, the related molecule SFRP2 is e xpressed specifically by cells of the inner nuclear layer, Thus, photorecep tors are likely to be bathed by two opposing gradients of SFRP molecules, C onsistent with SFRP5's postulated role in modulating Wnt signaling in the r etina, it inhibits the ability of Xwnt-8 mRNA to induce axis duplication in Xenopus embryos, The human SFRP5 gene consists of three coding exons and i t maps to chromosome 10q24.1; human SFRP2 maps to 4q31.3, Based on the biol ogy and complementary expression patterns of SFRP2 and SFRP5, we suggest th at they may be involved in determining the polarity of photoreceptor, and p erhaps other, cells in the retina.