Wnt_β-Catenin SignalingWnt_β-Catenin Signaling.pdf

Leading Edge Review Wnt/β-Catenin Signaling in Development and Disease 1, Hans Clevers * 1Hubrecht Laboratory and Utrecht University, Uppsalalaan 8, 3584CT, Utrecht, the Netherlands *Contact: clevers@niob.knaw.nl DOI 10.1016/j.cell.2006.10.018 A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades. Wnt genes encode small secreted proteins that are found in all animal genomes. Wnt signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues. The mouse wnt1 gene, originally named Int-1, was iden- The combined observations made in Drosophila and tified in 1982 by Nusse and Varmus as a preferential Xenopus delineated a highly conserved signaling path- integration site for the Mouse Mammary Tumor Virus way, activated by secreted Wnt proteins. Independent in virally induced breast tumors (Nusse and Varmus, of these studies, the adenomatous polyposis coli (APC) 1982). When sequenced, the Wnt1 proto-oncogene was gene was discovered in a hereditary cancer syndrome seen to encode a secreted protein that is cysteine rich. termed familial adenomatous polyposis (FAP) (Kinzler Subsequently, Drosophila wingless (wg), which controls et al., 1991; Nishisho et al., 1991). Soon after, the large segment polarity during larval development (Nüsslein- cytoplasmic APC protein was found to interact with Volhard and Wieschaus, 1980), was shown to be a fly β-catenin (R