Morpholinos for splice modificatio

Morpholinos for splice modification

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Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling
P.N. Adler, J. Charlton, J. Liu

Summary

The adult cuticular wing of Drosophila is covered by an array of distally pointing hairs that reveals the planar polarity of the wing. We report here that mutations in dachsous disrupt this regular pattern, and do so by affecting frizzled signaling. dachsous encodes a large membrane protein that contains many cadherin domains and dachsous mutations cause deformed body parts. We found that mutations in dachsous also result in a tissue polarity phenotype that at the cellular level is similar to frizzled, dishevelled and prickle, as many cells form a single hair of abnormal polarity. Although their cellular phenotype is similar to frizzled, dishevelled and prickle, dachsous mutant wings display a unique and distinctive abnormal hair polarity pattern including regions of reversed polarity. The development of this pattern requires the function of frizzled pathway genes suggesting that in a dachsous mutant the frizzled pathway is functioning - but in an abnormal way. Genetic experiments indicated that dachsous was not required for the intracellular transduction of the frizzled signal. However, we found that dachsous clones disrupted the polarity of neighboring wild-type cells suggesting the possibility that dachsous affected the intercellular signaling function of frizzled. Consistent with this hypothesis we found that frizzled clones in a dachsous mutant background displayed enhanced domineering non-autonomy, and that the anatomical direction of this domineering non-autonomy was altered in regions of dachsous wings that have abnormal hair polarity. The direction of this domineering nonautonomy was coincident with the direction of the abnormal hair polarity. We conclude that dachsous causes a tissue polarity phenotype because it alters the direction of frizzled signaling.