In the past we used mouse embryonic stem cells (mESCs) to distinguish between the requirements of β-catenin in functioning as a transcriptional co-activator and as a component of cell adherens junctions. mESCs deficient for β-catenin function show no self-renewing defects under standard conditions (LIF & Serum) and only minor cell adhesion defects (Figure 4a). However, these cells fail to differentiate into derivatives of all three germ layers and show massive cell adhesion defects during differentiation. Rescue experiments using a Tcf/Lef-signaling defective, but cell adhesion competent variant of β-catenin revealed a requirement for the cell adhesion function of β-catenin for the derivation of neurons (an ectodermal derivative) and for the definitive endoderm, while rescuing cell-adhesion did not influence mesoderm formation (Figure 4b) (Lyashenko et al., 2011). Hence, the function of β-catenin in cell-adhesion is probably playing are marginal role compared to its function as a transcriptional co-activator in the formation of mesoderm. We are now using a β-catenin allele that only maintains the cell-adhesion function of β-catenin, which allows us to distinguish between the requirements of the two distinct functions during embryonic skeletal development.