β-Catenin is a central component of both the cadherin- catenin cell adhesion complex and the Wnt signaling

β-catenin was originally identified complexed with the cell adhesion molecule (CAM) E-cadherin (Vestweber and Kemler, 1984; Ozawa et al., 1989; Nagafuchi and Takeichi, 1989). Subsequently, β-catenin was found to bind directly to the cytoplasmic domain of E-cadherin and to α-catenin, linking this adhesion complex to the actin cytoskeleton (Aberle et al., 1994; Aberle et al., 1996a; Hülsken et al., 1994; Jou et al., 1995; Rimm et al., 1995). Compelling evidence has since been provided that the E-cadherin/catenin complex is crucial for epithelial cell polarity and function (Aberle et al., 1996b). Furthermore, mutations in components of the E-cadherin/ catenin complex are correlated with increased invasiveness and metastasis of tumor cells (Berx et al., 1998). The homology of β-catenin with Drosophila Armadillo (Arm) suggested the now well-established fact that β-catenin – like Arm – is part of the Wingless/Wnt (Wg/Wnt) signaling pathway (McCrea et al., 1991; Butz et al., 1992). Wnts act as signaling molecules and are implicated in many developmental processes, including cell fate specification, polarity, migration and proliferation (Gonzalez et al., 1991; Jue et al., 1992; Cadigan and Nusse, 1997). Upon binding to cell surface receptors, Wnts initiate an intracellular cascade that, via several intermediate steps, leads to the translocation of βcatenin to the nucleus. There, together with transcription factors of the T-cell factor/lymphoid enhancer-binding factor 1 (TCF/LEF1) family, β-catenin regulates expression of target genes (reviewed by Eastman and Grosschedl, 1999; Miller et al., 1999). Many vertebrate Wnts are expressed in the embryonic central nervous system (CNS) (Parr et al., 1993; Hollyday et al., 1995). In the mouse, beginning 8.5 days post coitum (dpc), Wnt1 and Wnt3a are expressed along the dorsal midline of the neural tube, suggesting a role in regional specification of the neural tube (Roelink and Nusse, 1991; Parr et al., 1993). By 9.5 dpc at least seven Wnts are expressed in the presumptive brain and spinal cord, including Wnt1, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt7a and Wnt7b (Parr et al., 1993; Salinas and Nusse, 1992), suggesting multiple and complex patterns of Wnt signaling. Wnt1 plays an important role in the anterior-posterior 1253 Development 128, 1253-1264 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV2678