The function of the frizzled pathway in the Drosophila wing is dependent on inturned and fuzzy

The Drosophila epidermis is characterized by a dramatic planar or tissue polarity. The frizzled pathway has been shown to be a key regulator of planar polarity for hairs on the wing, ommatidia in the eye, and sensory bristles on the notum. We have investigated the genetic relationships between putative frizzled pathway downstream genes inturned, fuzzy, and multiple wing hairs (inturned-like genes) and upstream genes such as frizzled, prickle, and starry night (frizzled-like genes). Previous data showed that the inturned-like genes were epistatic to the frizzled-like genes when the entire wing was mutant. We extended those experiments and examined the behavior of frizzled clones in mutant wings. We found the domineering nonautonomy of frizzled clones was not altered when the clone cells were simultaneously mutant for inturned, multiple wing hairs, or dishevelled but it was blocked when the entire wing was mutant for inturned, fuzzy, multiple wing hairs, or dishevelled. Thus, for the domineering nonautonomy phenotype of frizzled, inturned and multiple wing hairs are needed in the responding cells but not in the clone itself. Expressing a number of frizzled pathway genes in a gradient across part of the wing repolarizes wing cells in that region. We found inturned, fuzzy, and multiple wing hairs were required for a gradient of frizzled, starry night, prickle, or spiny-legs expression to repolarize wing cells. These data argue that inturned, fuzzy, and multiple wing hairs are downstream components of the frizzled pathway. To further probe the relationship between the frizzled-like and inturned-like genes we determined the consequences of altering the activity of frizzled-like genes in wings that carried weak alleles of inturned or fuzzy. Interestingly, both increasing and decreasing the activity of frizzled and other upstream genes enhanced the phenotypes of hypomorphic inturned and fuzzy mutants. We also examined the relationship between the frizzled-like and inturned-like genes in other regions of the fly. For some body regions and cell types (e.g., abdomen) the inturned-like genes were epistatic to the frizzled-like genes, but in other body regions (e.g., eye) that was not the case. Thus, the genetic control of tissue polarity is body region specific.