Wnt signaling: a common theme in animal development (original) (raw)

  1. Ken M. Cadigan and
  2. Roel Nusse1
  3. Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University Medical Center, Stanford, California 94305-5323 USA

Wnt proteins are now recognized as one of the major families of developmentally important signaling molecules, with mutations in Wnt genes displaying remarkable phenotypes in the mouse, Caenorhabditis elegans, and Drosophila. Among functions provided by Wnt proteins are such intriguing processes as embryonic induction, the generation of cell polarity, and the specification of cell fate. Until recently, our knowledge of the molecular mechanism of Wnt signaling was very limited, but over the past year, several major gaps have been filled. These include the identification of cell-surface receptors and a novel mechanism of relaying the signal to the cell nucleus. In addition, several components of Wnt signaling are implicated in the genesis of human cancer. These insights have come from different corners of the animal kingdom and have converged on a common pathway. At this junction in this rapidly evolving field, we review our current understanding of Wnt function and signaling mechanisms, doing so in a comparative approach. We have put emphasis on the latest findings, highlighting novelty and underscoring questions that remain. For additional literature, we refer to several previous reviews (McMahon 1992; Nusse and Varmus 1992;Klingensmith and Nusse 1994; Miller and Moon 1996; Moon et al. 1997). We have limited the number of references, particularly in the tables. Fully referenced forms of these tables can be found on the Wnt homepage (http://www-leland.stanford.edu/\~rnusse/wntwindow.html).

The Wnt Family

Wnt genes are defined by sequence homology to the original members Wnt_-1 in the mouse (first called_int_-1; Nusse and Varmus 1982; Van Ooyen and Nusse 1984) and_wingless (wg) in Drosophila (Cabrera et al. 1987; Rijsewijk et al. 1987). They encode secreted glycoproteins, usually 350–400 amino acids in length. Homologous genes have been found in increasing numbers in organisms ranging from mammals to the nematode C. …