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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Dev+Dyn 2014 ; 243 (9): 1095-105 Nephropedia Template TP
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Concentration-dependent effects of WNTLESS on WNT1/3A signaling #MMPMID24866848
Dev Dyn 2014[Sep]; 243 (9): 1095-105 PMID24866848show ga
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/?-catenin pathway in HEK293T cells, while overexpression of higher levels of WLS inhibits the Wnt/?-catenin pathway in these cells. Similarly, overexpressed WLS inhibits the Wnt/?-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 ?-catenin-dependent transcription. Conclusion: Our results show that overexpression of WLS inhibits Wnt/?-catenin signaling in the spinal cord. As the activation of the Wnt/?-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.
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Dev+Dyn 2014 ; 243 (9): 1095-105
