The Wnt-1 protooncogene was identified in several indepen- dently arising mammary tumors in which proviral insertion of Mouse Mammary Tumor Virus (MMTV) resulted in activation and ectopic expression of an apparently normal Wnt-1 gene

The Wnt-1 protooncogene was identified in several independently arising mammary tumors in which proviral insertion of Mouse Mammary Tumor Virus (MMTV) resulted in activation and ectopic expression of an apparently normal Wnt-1 gene product (Nusse and Varmus, 1982; Nusse et al., 1984; van Ooyen and Nusse, 1984). Cell culture (Brown et al., 1986; Rijsewijk et al., 1987; Jue et al., 1992) and transgenic mouse (Tsukamoto et al., 1988; Kwan et al., 1992) studies have clearly demonstrated that ectopic expression of Wnt-1 in mammary epithelium leads to morphological transformation in vitro and dramatic hyperplasia in vivo. Thus, a causal relationship between ectopic expression of Wnt-1 and the development of mammary adenocarcinomas has been established (reviewed by Nusse and Varmus, 1992). More recently, studies in a number of developmental systems, most notably Drosophila and the mouse, have started to address the normal role of Wnt-1. Wnt-1 in the mouse, and its Drosophila counterpart the segment polarity gene wingless (wg), encode cysteine-rich, secreted glycoproteins (Papkoff et al., 1987; Brown et al., 1987; van den Heuvel et al., 1989; Gonzalez et al., 1991) which are members of a large family of putative signaling molecules (reviewed in McMahon, 1992; Nusse and Varmus, 1992). In Drosophila, analysis of multiple alleles indicates that wg is required throughout embryonic and larval development (Baker, 1988). The best studied aspect of wg-mediated regulation lies in patterning of the embryonic segment where wg is necessary to maintain expression of the homeobox-containing transcription factor, engrailed, in posterior cells (DiNardo et al., 1988; Martinez-Arias et al., 1988; Heemskerk et al., 1991; Gonzalez et al., 1991; Bejsovec and Martinez-Arias, 1991) and in the subsequent regulation of cell fate choices adopted by these cells (Dougan et al., 1991). In the absence of correct wg signaling, posterior pattern elements in each of the segments are lost, partly by cell death (Perrimon and Mahowald, 1987), and partly by cells adopting more anterior fates (NüssleinVolhard and Wieschaus, 1980; Dougan et al., 1991). Although later functions are less well understood, wg appears to be essential for development and/or patterning of the limb (Cohen, 1990; Couso et al., 1993; Struhl and Basler, 1993), wing (Couso et al., 1993; Williams et al., 1993) and Malpighian tubules (Skaer and Martinez-Arias, 1992). Thus, wg is used in many different contexts during insect development. In contrast, in the mouse and all other vertebrate embryos studied to date, Wnt-1 is only expressed during development in the central nervous system (CNS; Wilkinson et al., 1987; Davis et al., 1988; Molven et al., 1991; McMahon et al., 1992; 2213 Development 120, 2213-2224 (1994) Printed in Great Britain © The Company of Biologists Limited 1994