Pax6-dependent, but β-catenin-independent, function of Bcl9 proteins in mouse lens development

Bcl9 and Bcl9l (Bcl9/9l) encode Wnt signaling components that mediate the interaction between beta-catenin and Pygopus (Pygo) via two evolutionarily conserved domains, HD1 and HD2, respectively. We generated mouse strains lacking these domains to probe the beta-catenin-dependent and beta-catenin-independent roles of Bcl9/9l and Pygo during mouse development. While lens development is critically dependent on the presence of the HD1 domain, it is not affected by the lack of the HD2 domain, indicating that Bcl9/9l act in this context in a beta-catenin-independent manner. Furthermore, we uncover a new regulatory circuit in which Pax6, the master regulator of eye development, directly activates Bcl9/9l transcription.