TISSUE POLARITY POINTS FROM CELLS THAT HAVE HIGHER FRIZZLED LEVELS TOWARDS CELLS THAT HAVE LOWER FRIZZLED LEVELS

Background: The frizzled (fi) gene of Drosophila encodes the founding member of the large family of receptors for the Wnt family of signalin g molecules, It was originally studied in the adult epidermis, where i t plays a key role in the generation of tissue polarity. Mutations in components of the fi signal transduction pathway disrupt tissue polari ty; on the wing, hairs normally point distally but their polarity is a ltered by these mutations. Results: We devised a method to induce a gr adient of fi expression with the highest levels near the distal wing t ip. The result was a large area of proximally pointing hairs in this r egion, This reversal of polarity was seen when fz expression was induc ed just before the start of hair morphogenesis when polarity is establ ished, suggesting that the gradient of Fz protein acted fairly directl y to reverse hair polarity, A similar induction of the dishevelled (ds h) gene, which acts cell autonomously and functions downstream of fi i n the generation of tissue polarity, resulted in a distinct tissue pol arity phenotype, but no reversal of polarity; this argues that it sign aling was required for polarity reversal. Furthermore, the finding tha t functional dsh was required for the reversal of polarity argues that the reversal requires normal fi signal transduction. Conclusions: The data suggest that cells sense the level of Fz protein on neighboring cells and use this information in order to polarize themselves, A pola rizing signal is transmitted from cells with higher Fz levels to cells with lower levels. Our observations enable us to propose a general me chanism to explain how Wnts polarize target cells.