The Balance Between the Novel Protein Target of Wingless and the Drosophila Rho-Associated Kinase Pathway Regulates Planar Cell Polarity in the Drosophila Wing

Abstract

Planar cell polarity (PCP) signaling is mediated by the serpentine receptor Frizzled (Fz) and transduced by Dishevelled (Dsh). Wingless (Wg) signaling utilizes Drosophila Frizzled 2 (DFz2) as a receptor and also requires Dsh for transducing signals to regulate cell proliferation and differentiation in many developmental contexts. Distinct pathways are activated downstream of Dsh in Wg-and Fz-signaling pathways. Recently, a number of genes, which have essential roles as downstream components of PCP signaling, have been identified in Drosophila. They include the small GTPase RhoA/Rho1, its downstream effector Drosophila rho-associated kinase (Drok), and a number of genes such as inturned (in) and fuzzy ( fy), whose biochemical functions are unclear. RhoA and Drok provide a link from Fz/Dsh signaling to the modulation of actin cytoskeleton. Here we report the identification of the novel gene target of wingless (tow) by enhancer trap screening. tow expression is negatively regulated by Wg signaling in wing imaginal discs, and the balance between tow and the Drok pathway regulates wing-hair morphogenesis. A loss-of-function mutation in tow does not result in a distinct phenotype. Genetic interaction and gain-of-function studies provide evidence that Tow acts downstream of Fz/Dsh and plays a role in restricting the number of hairs that wing cells form.

Overexpression of CTHRC1 in Hepatocellular Carcinoma Promotes Tumor Invasion and Predicts Poor Prognosis

“…Planar cell polarity signaling regulates the establishment of polarity within the plane of the epithelium and allows cells to obtain directional information during embryogenesis [22]. One of the major components of the planar cell polarity pathway is the activation of small GTPases, including RhoA and Rac1, and their downstream protein kinases, ROCK and JNK, respectively, to regulate cytoskeletal reorganization [23]. Hence, by secreting CTHRC1 into its microenviroment, cancer cells stimulate their own motility and that of adjacent cancer cells by activating RhoA signaling.…”

Serrano (Sano) Functions with the Planar Cell Polarity Genes to Control Tracheal Tube Length

“…Since it is difficult to distinguish w + / w + versus w + / w − in thin sections, however, we chose only eyes with large mutant clones and adjacent w − /w − twin spots for sectioning. Fixation and semi-thin sectioning of the adult eyes were slightly modified from [93]. Sections from at least five independent eyes were analyzed for each genotype.…”

Hedgehog signaling and gastrointestinal cancer

“…Tow is a Drosophila homolog of a previously uncharacterized protein family that controls the availability of Smo by regulating the degradation of lipophorin particles [82]. Homologs of Tow have only been identified in insects [83] however; proteins with similar functions may exist in vertebrates. Tow is suppressed by wingless, and its over-expression causes planar cell polarity defects [83].…”

“…Homologs of Tow have only been identified in insects [83] however; proteins with similar functions may exist in vertebrates. Tow is suppressed by wingless, and its over-expression causes planar cell polarity defects [83]. Thus at least in insects, Hh signaling appears to be suppressed by the Wnt pathway.…”