Planar cell polarity signaling in Drosophila requires the receptor Frizzled and the cytoplasmic proteins Dishevelled and Prickle. From initial, symmetric subcellular distributions in pupal wing cells, Frizzled and Dishevelled become highly enriched at the distal portion of the cell cortex. We describe a Prickle-dependent intercellular feedback loop that generates asymmetric Frizzled and Dishevelled localization. In the absence of Prickle, Frizzled and Dishevelled remain symmetrically distributed. Prickle localizes to the proximal side of pupal wing cells and binds the Dishevelled DEP domain, inhibiting Dishevelled membrane localization and antagonizing Frizzled accumulation. This activity is linked to Frizzled activity on the adjacent cell surface. Prickle therefore functions in a feedback loop that amplifies differences between Frizzled levels on adjacent cell surfaces.

Infection by HTLV-1 has been correlated with the appearance of various proliferative or degenerative diseases. Some of these disorders have been observed in transgenic mice expressing the Tax protein, which is known to transactivate various viral and cellular promoters through interactions with several transcription factors. In this study we show that the C-terminus of this viral oncoprotein represents a motif permitting binding of Tax to the PDZ domains of several cellular proteins. A two-hybrid screen with Tax as bait indeed yielded complementary DNAs coding for six proteins including PDZ domains. Two of them correspond to truncated forms of the PSD-95 and b1-syntrophin proteins, another clone codes for a protein homologous to the product of the C. elegans gene lin-7. The other three clones code for new human members of the PDZ family of cellular proteins. The interaction of Tax with the products of these clones was con®rmed by immunoprecipitation assays in mammalian cells, and analysis of various mutants of Tax established the importance of the Cterminal amino acids for several of these interactions. These data suggest that Tax could perturb the normal function of targeted cellular proteins by strongly interacting with their PDZ domains.

In Drosophila embryos the protein Naked cuticle (Nkd) limits the effects of the Wnt signal Wingless (Wg) during early segmentation. nkd loss of function results in segment polarity defects and embryonic death, but how nkd affects Wnt signaling is unknown. Using ectopic expression, we find that Nkd affects, in a cell-autonomous manner, a transduction step between the Wnt signaling components Dishevelled (Dsh) and Zeste-white 3 kinase (Zw3 Secreted Wnt proteins act as potent mitogens and cellfate regulators in organisms ranging from nematodes to humans. In vertebrates they specify cell fate and control growth in a variety of developmental processes, including brain development, limb formation, axis specification, and gastrulation (for review, see Cadigan and Nusse 1997). In the fruit fly Drosophila, the Wnt protein Wingless (Wg) establishes segment polarity during embryogenesis and is involved in multiple additional patterning events throughout later development (Cadigan and Nusse 1997). wg is first expressed in the developing epidermis in stripes just anterior to cells expressing the engrailed (en) gene and is necessary to maintain en transcription (DiNardo et al. 1988;Martinez Arias et al. 1988). hedgehog (hh) is expressed in the en-expressing cells and positively regulates wg expression in the anterior cells (Ingham et al. 1991;Lee et al. 1992). This positive-feedback loop establishes parasegmental boundaries, the first evidence of the metameric organization of the embryo, between wg-and en/hh-expressing cells. At later stages of embryonic development, a tight balance between Wg and other signaling pathways, such as the Drosophila epidermal growth factor receptor (EGFR), determines whether epidermal cells secrete either naked (smooth) cuticle or hair-like structures called denticles (Dougan and DiNardo 1992;O'Keefe et al. 1997;Szuts et al. 1997). In the absence of wg function, embryos are covered with a lawn of denticles, whereas otherwise wild-type embryos exposed to excess Wg produce a naked cuticle (Martinez Arias et al. 1988;Noordermeer et al. 1992).Genetic and biochemical studies have lead to the identification of the key components of the Wnt/Wg pathway and have uncovered some of the molecular events that are involved in signal transduction (Fig. 1A). Wg binds 7-pass transmembrane receptors of the frizzled family (Fz or Dfz2), which, in turn, activate the cytoplasmic protein Dishevelled (Dsh; Theisen et al. 1994;Bhanot et al. 1996). Dsh antagonizes the activity of a large protein complex that, in the absence of Wg signal, results in Armadillo (Arm)/␤-catenin phosphorylation and subsequent degradation by the ubiquitin-proteasome pathway (Yost et al. 1996;Aberle et al. 1997;Pai et al. 1997). This multiprotein complex includes Zw3/Glycogen synthase kinase 3␤ (Gsk3␤), Adenomatous Polyposis Coli (APC), Axin, and Arm/␤-catenin. Axin constitutes the core of this complex, al-