03-P120 Fat4 and Dachsous1 regulate the apical membrane organization in the mouse cerebral cortex

signal transducer of canonical Wnt signaling and activates canonical Wnt target genes. b-catenin null mice die at E7.5. Since the conditional loss of b-catenin function in vivo does not distinguish between adhesion and signaling, it is unclear whether the knock-out phenotype is due to defects in signaling, adhesion or both. Our aim is to generate conditional alleles for functionally mutant b-catenin isoforms. With the help of such signaling or adhesion impaired isoforms, we want to decipher the functional dualism of b-catenin in vivo. We will conditionally express the b-catenin from the ubiquitously active ROSA26 locus, and simultaneously delete endogenous b-catenin alleles. However, before analyzing mutant b-catenin isoforms, we have to test the suitability of our experimental approach. In a proof of principle experiment, we are studying whether the b-catenin knock out phenotype can be rescued by expressing wild-type bcatenin from the ROSA26 locus. In vitro, we can show that targeted b-catenin null cells, derived from ES cells, express b-catenin on the membrane and display wild-type ES cell morphology. Furthermore, we successfully generated mice carrying the transgene. Currently, we are investigating the usability of different Cre-mouse lines in order to generate b-catenin null mice, which express wild-type b-catenin from the ROSA26 locus. Ultimately, we want to substitute the wild-type gene with our mutant isoforms and decipher the functions of b-catenin in vivo.