E-cadherin regulates the stability and transcriptional activity of beta-catenin in mouse embryonic stem cells

E-CADHERIN is abundantly expressed in embryonic stem cells (ESCs) and plays an important role in the maintenance of cell-cell adhesions. However, the exact function of this molecule beyond cell adhesion, in the context of cell fate decisions is largely unknown. Using mouse ESCs (mESCs), we report that E-CADHERIN and -CATENIN interact at the membrane and continue to do so upon internalization within the cell. Knockout of Cdh1 in mouse ESCs resulted in a failure to form tight colonies, with altered expression of differentiation markers, including retention of pluripotency factor expression. Interestingly, these Cdh1-/- mESCs showed a dramatic reduction in the amount of -CATENIN present, and its associated transcriptional activity. Transcriptional profiling of Cdh1-/- mESCs displayed a significant alteration in the expression of a subset of -CATENIN targets, in a cell-state dependent manner. While treatment with a pharmacological inhibitor against GSK3 could rescue levels of -CATENIN in Cdh1-/- mESCs, expression of downstream targets remained largely unaffected, indicating an additional layer of regulation within this subset. Together, our results reveal the existence of a cell-state-dependent regulation of -CATENIN and its transcriptional targets in an E-CADHERIN dependent manner. Our findings further hint at hitherto unknown roles played by E-CADHERIN in regulating the activity of -CATENIN. 3 replicates of WT V6.5 mESCs vs Cdh1-/- V6.5 cells