Wnt/beta-catenin signaling regulates expression of PRDC, an antagonist of the BMP-4 signaling pathway.

To identify novel target genes regulated by Wnt/beta-catenin signaling, microarray analysis was performed with L929 fibroblast cells. In this report, we show that the expression of PRDC (Protein Related to DAN and Cerberus), previously known as an antagonist of Nodal, BMP (bone morphogenetic protein), and Wnt signals, is specifically induced by Wnt/beta-catenin signaling, and also show that the transcriptional activation is mediated in a Tcf/LEF-independent manner. The PRDC induced by Wnt/beta-catenin does not inhibit Wnt signaling, but does inhibit BMP-4 signaling. The inhibition of BMP-4-induced reporter activity by the treatment of conditioned media from beta-catenin(S37A)-expressing cells suggests that the PRDC induced by beta-catenin is secreted outside of cells and antagonizes BMP-4 signaling. We propose that PRDC might serve as a mediator to antagonize BMP-4 signaling by Wnt.