Differential Recruitment of Dishevelled Provides Signaling Specificity in the Planar Cell Polarity and Wingless Signaling Pathways in Drosophila, Planar Cell Polarity (pcp) Signaling Is Mediated by the Receptor Frizzled (fz) and Transduced by Dishevelled (dsh). Wingless (wg) Signaling Also Requires
Differential Recruitment of Dishevelled Provides Signaling Specificity in the Planar Cell Polarity and Wingless Signaling Pathways in Drosophila, Planar Cell Polarity (pcp) Signaling Is Mediated by the Receptor Frizzled (fz) and Transduced by Dishevelled (dsh). Wingless (wg) Signaling Also Requires
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J. Axelrod;Jeffrey R. Miller;J. Shulman;R. Moon;N. Perrimon
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作者：
J. Axelrod;Jeffrey R. Miller;J. Shulman;R. Moon;N. Perrimon
Drosophila Dishevelled (Dsh) was initially identified for its role in transducing the planar cell polarity (PCP; also known as tissue polarity) signal in developing imaginal Dsh was shown subsequently to trans-duce an additional signal mediated by Wingless (Wg) (Klingensmith et al. 1994). We have investigated how Dsh functions in PCP signaling and whether it has the same or different function in Wg signaling. PCP signaling controls the polarity of epithelial cells within a plane orthogonal to their apical–basal axis. One manifestation of this cellular polarity is the oriented organization of trichomes (cell hairs). In wild-type flies, the cell hair arising from each cell's distal vertex contributes to a parallel and specifically oriented array (Fig. 5A, below). Mutations in dsh, as well as additional genes including frizzled (fz), prickle (pk), inturned (in), fuzzy (fy), multiple wing hairs (mwh), and others all disrupt the polarity of the trichomes. The resulting mutant phenotypes include swirls and distortions of the hair polarity pattern, and in some instances, more than one trichome per cell (e.g., Fig. 5B, below). A putative signal transduc-tion pathway has been proposed (Krasnow et al. 1995), which serves to polarize cells, allowing them to distinguish one side of the cell from the other, and to propagate this information from cell to cell. In this pathway, Fz, a seven-transmembrane protein (without apparent primary sequence homology to the G-protein-coupled receptors) acts as a receptor (Vinson et al. 1989; Adler et al. 1990), functioning upstream of Dsh. Dsh then antagonizes the activities of Fy, In (both novel transmembrane proteins; Park et al. 1996; Collier and Gubb 1997), and Mwh, which are in turn proposed to regulate the cyto-skeletal apparatus responsible for control of PCP. Mutations in RhoA affect this process (Strutt et al. 1997), and experiments with dominant-negative mutants have implicated Cdc42 and Rac1 (Eaton et al. 1995, 1996) as additional effectors. Pk is proposed to function either in transmission of the signal to adjacent cells, or in interpretation of the directionality of the signal. Thus far, no ligand for the PCP pathway has been identified. Although a tentative signal transduction pathway has been proposed, the mechanism by which asymmetry is established in the responding cells is not understood.
