Many developing and adult tissues are comprised of polarized epithelia. Pro
teins that are asymmetrically distributed in these cells are thought to be
localized by protein trafficking. Here we show that the distribution and fu
nction of the signaling protein Wingless is predetermined by the subcellula
r localization of its mRNA. High-resolution in situ hybridization reveals a
pical transcript localization in the majority of tissues examined. This loc
alization is mediated by two independently acting elements in the 3' UTR. R
eplacement of these elements with non- or basolaterally localizing elements
yields proteins with altered intracellular and extracellular distributions
and reduced signaling activities. This novel aspect of the wingless signal
ing pathway is conserved and may prove to be a mechanism used commonly for
establishing epithelial cell polarity.