Rabbit Anti-Human FZD10 (internal) Polyclonal antibody

Background: WNTLESS (WLS) is a multi-transmembrane protein that transports Wnt ligands from the Golgi to the cell surface. Although WLS loss-of-function experiments in the developing central nervous system reveal phenotypes consistent with defects in WNT1 and WNT3A signaling, data from complementary gain-of-function experiments have not yet been reported. Here, we report the phenotypic consequences of WLS overexpression in cultured cells and in the developing chick spinal cord. Results: Overexpression of small amounts of WLS along with either WNT1 or WNT3A promotes the Wnt/beta-catenin pathway in HEK293T cells, while overexpression of higher levels of WLS inhibits the Wnt/beta-catenin pathway in these cells. Similarly, overexpressed WLS inhibits the Wnt/beta-catenin pathway in the developing spinal cord, as assessed by cell proliferation and specification. These effects appear to be Wnt-specific as overexpression of WLS inhibits the expression of FZD10, a target of beta-catenin-dependent transcription. Conclusions: Our results show that overexpression of WLS inhibits Wnt/beta-catenin signaling in the spinal cord. As the activation of the Wnt/beta-catenin pathway in the spinal cord requires WNT1 or WNT3A, our results are consistent with a model in which the relative concentration of WLS to Wnt regulates WNT1/3A signaling in the developing spinal cord. (C) 2014 Wiley Periodicals, Inc.