ACCUMULATION OF ARMADILLO INDUCED BY WINGLESS, DISHEVELLED, AND DOMINANT-NEGATIVE ZESTE-WHITE-3 LEADS TO ELEVATED DE-CADHERIN IN DROSOPHILACLONE-8 WING DISC CELLS

Drosophila genetic studies suggest that in the Wingless (Wg) signaling pathway, the segment polarity gene products, Dishevelled (Dsh), Zeste -white 3 (ZW-3), and Armadillo (Arm), work sequentially; wg and dsh ne gatively regulate zw-3, which in turn down-regulates arm. To biochemic ally analyze interactions between the Wg pathway and Drosophila E-cadh erin (DE-cadherin) which bind to Arm, we overexpressed Dsh, ZW-3, and Arm, in the Drosophila wing disc cell Line, clone 8, which responds to Wg signal. Dsh overexpression led to accumulation of Arm primarily in the cytosol and elevation of DE-cadherin at cell junctions. Overexpre ssion of wildtype and dominant-negative forms of ZW-3 decreased and in creased Arm levels, respectively, indicating that modulation in zw-3 a ctivity negatively regulates Arm levels. Overexpression of an Arm muta nt with an aminoterminal deletion elevated DE-cadherin levels, suggest ing that Dsh-induced DE-cadherin elevation is caused by the Arm accumu lation induced by Dsh. Moreover, the Dsh-, dominant-negative ZW-3-, an d truncated Arm-induced accumulation of DE-cadherin protein was accomp anied by a marked increase in the steady-state levels of DE-cadherin m RNA, suggesting that transcription of DE-cadherin is activated by Wg s ignaling. In addition, overexpression of DE-cadherin elevated Arm leve ls by stabilizing Arm at cell-cell junctions.