Cloning and Characterization of a Secreted Frizzled-Related Protein that is Expressed by the Retinal Pigment Epithelium

Abstract

The Wnt/frizzled cell signaling pathway has been implicated in the determination of polarity in a number of systems, including the Drosophila retina. The vertebrate retina develops from an undifferentiated neuroepithelium into an organized and laminated structure that demonstrates a high degree of polarity at both the tissue and cellular levels. In the process of searching for molecules that are preferentially expressed by the vertebrate retinal pigment 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 expressed in the pancreas. Within the retina, the related molecule SFRP2 is expressed specifically by cells of the inner nuclear layer. Thus, photoreceptors are likely to be bathed by two opposing gradients of SFRP molecules. Consistent with SFRP5 's postulated role in modulating Wnt signaling in the retina, 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 it maps to chromosome 10q24.1; human SFRP2 maps to 4q31.3. Based on the biology and complementary expression patterns of SFRP2 and SFRP5, we suggest that they may be involved in determining the polarity of photoreceptor, and perhaps other, cells in the retina.

Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina

“…However, Wnt genes are expressed at very low levels compared with Mfz or Sfrp genes. In contrast to Chang et al, who showed Sfrp-2 expression in the INL of the bovine retina (Chang et al, 1999), we find that Sfrp-2 expression is down-regulated in the murine retina after P7. Similarly, Rattner et al (1997) reported that Sfrp-1 transcripts are restricted to the ciliary margin and lens in the adult mouse eye; however, we find that Sfrp-1 transcripts are also present in the neural retina at this stage.…”

“…The expression of Mfz and Sfrp transcripts in the adult eye has been reported previously Rattner et al, 1997;Chang et al, 1999), and we extend those findings by showing the localization of Wnts, in the mouse neural retina at perinatal and adult stages. However, Wnt genes are expressed at very low levels compared with Mfz or Sfrp genes.…”

Transcript analyses of stromal cell derived factors (SDFs): SDF-2, SDF-4 and SDF-5 reveal a different pattern of expression and prognostic association in human breast cancer

“…These proteins are receptors for Wnt family members. The function of SDF-5 is not clear, although it has been suggested that when over-expressed in breast cancer cells it regulates apoptosis of the cells, possibly by way of ß-catenin (22,23). Little is available with regard to the expression of these new SDFs in cancer.…”

Transcriptional regulation of the promoter of the rat frizzled related protein gene by CREB

“…Secretory Frps were independently isolated from bovine, Xenopus, mouse, rat and human by different laboratories (Hoang et al, 1996; Leyns et al, 1997; Rattner et al, 1997;Wang et al, 1997;Wolf et al, 1997;Zhou et al, 1998;Chang et al, 1999;Yam et al, 1999;Katoh, 2001). The precise interaction of each Frp protein in modulating Wnt signaling remains to be elucidated.…”