MUTATIONS IN THE CADHERIN SUPERFAMILY MEMBER GENE DACHSOUS CAUSE A TISSUE POLARITY PHENOTYPE BY ALTERING FRIZZLED SIGNALING

The adult cuticular wing of Drosophila is covered by an array of dista lly pointing hairs that reveals the planar polarity of the wing. We re port here that mutations in dachsous disrupt this regular pattern, and do so by affecting frizzled signaling. dachsous encodes a large membr ane protein that contains many cadherin domains and dachsous mutations cause deformed body parts. We found that mutations in dachsous also r esult in a tissue polarity phenotype that at the cellular level is sim ilar to frizzled, dishevelled and prickle, as many cells form a single hair of abnormal polarity. Although their cellular phenotype is simil ar to frizzled, dishevelled and prickle, dachsous mutant wings display a unique and distinctive abnormal hair polarity pattern including reg ions of reversed polarity. The development of this pattern requires th e function of frizzled pathway genes suggesting that in a dachsous mut ant the frizzled pathway is functioning - but in an abnormal way. Gene tic experiments indicated that dachsous was not required for the intra cellular transduction of the frizzled signal. However, we found that d achsous clones disrupted the polarity of neighboring wildtype cells su ggesting the possibility that dachsous affected the intercellular sign aling function of frizzled. Consistent with this hypothesis we found t hat frizzled clones in a dachsous mutant background displayed enhanced domineering non-autonomy, and that the anatomical direction of this d omineering non-autonomy was altered in regions of dachsous wings that have abnormal hair polarity. The direction of this domineering nonauto nomy was coincident with the direction of the abnormal hair polarity. We conclude that dachsous causes a tissue polarity because it alters t he direction of frizzled signaling.