Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
In Drosophila, planar cell polarity (PCP) signaling is mediated by the receptor Frizzled (Fz) and transduced by Dishevelled (Dsh). Wingless (Wg) signaling also requires Dsh and may utilize DFz2 as a receptor. Using a heterologous system, we show that Dsh is recruited selectively to the membrane by Fz but not DFz2, and this recruitment depends on the DEP domain but not the PDZ domain in Dsh. A mutation in the DEP domain impairs both membrane localization and the function of Dsh in PCP signaling, indicating that translocation is important for function. Further genetic and molecular analyses suggest that conserved domains in Dsh function differently during PCP and Wg signaling, and that divergent intracellular pathways are activated. We propose that Dsh has distinct roles in PCP and Wg signaling. The PCP signal may selectively result in focal Fz activation and asymmetric relocalization of Dsh to the membrane, where Dsh effects cytoskeletal reorganization to orient prehair initiation.
???displayArticle.pubmedLink???
9716412
???displayArticle.pmcLink???PMC317102 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Figure 1. DshâGFP localizes to the membrane and filopodia in response to Fz in Xenopus animal cap cells. (A) DshâGFP (green)
localizes in the cytoplasm in an apparent association with intracellular vesicles (Texas Red phalloidin labels the cell cortex). (B) In
response to Fz, DshâGFP redistributes to the plasma membrane. (C) Fz localizes predominantly to the plasma membrane in the
presence (shown) or absence (not shown) of DshâGFP. (D, D8) DshâGFP colocalizes with Fz at the plasma membrane. Yellow staining
represents colocalization of DshâGFP (green from B) and Fz (red from C) and is marked by an arrow in D8. However, regions of the
plasma membrane are also stained only by DshâGFP or Fz, demonstrating that the colocalization of DshâGFP and Fz is not absolute
(arrowheads in D8). (EâG) In response to Fz, DshâGFP also accumulates in filopodia that extend from the free surface of the animal cap
cells (arrowheads). These filopodia contain actin (stained with phalloidin; arrowhead in G8) but lack Fz (note lack of yellow staining
in filopodia in F). (H,I) In contrast to the effects of Fz on the localization of DshâGFP, neither DFz2 (H) nor the combination of DFz2
and Wg (I) results in a change in the localization of DshâGFP (DshâGFP = green). Texas Red phalloidin was used to visualize cell
outlines in A, H, and I, and the filopodium in G8.
Figure 2.
Analysis of Dsh domains required for Fz-dependent relocalization of Dsh in Xenopus animal cap cells. (A) Dsh(ÎbPDZ)âGFP localizes to the cytoplasm in a punctate pattern. (B) In response to Fz, Dsh(ÎbPDZ)âGFP relocalizes to the plasma membrane (shown) and is also present in filopodia (not shown). (C) Dsh(ÎDIX)âGFP does not display a punctate pattern and instead is distributed diffusely throughout the cytoplasm (but is excluded from yolk granules). (D) In response to Fz, Dsh(ÎDIX)âGFP relocalizes to the plasma membrane (shown) and is also present in filopodia (not shown). (E) Dsh(ÎDEP)âGFP localizes to the cytoplasm in a punctate pattern. (F) Dsh(ÎDEP)âGFP, however, does not relocalize to the plasma membrane in response to Fz and displays a punctate pattern similar to that seen in the absence of Fz. (G) Dsh(DEP+) is diffusely cytoplasmic in the absence of Fz, and is sufficient to promote membrane localization in the presence of Fz (H). Texas Red phalloidin was used to visualize cell outlines in A, C, E,and G.
Adler,
Tissue polarity points from cells that have higher Frizzled levels towards cells that have lower Frizzled levels.
1997, Pubmed
Adler,
Tissue polarity points from cells that have higher Frizzled levels towards cells that have lower Frizzled levels.
1997,
Pubmed
Adler,
The genetic control of tissue polarity in Drosophila.
1992,
Pubmed
Adler,
Molecular structure of frizzled, a Drosophila tissue polarity gene.
1990,
Pubmed
Axelrod,
Interaction between Wingless and Notch signaling pathways mediated by dishevelled.
1996,
Pubmed
Bejsovec,
Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface.
1995,
Pubmed
Bhanot,
A new member of the frizzled family from Drosophila functions as a Wingless receptor.
1996,
Pubmed
Boutros,
Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling.
1998,
Pubmed
Brand,
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
1993,
Pubmed
Brand,
Ectopic expression in Drosophila.
1994,
Pubmed
Cadigan,
Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing.
1998,
Pubmed
Cadigan,
Wnt signaling: a common theme in animal development.
1997,
Pubmed
,
Xenbase
Chakrabarti,
Secretory and inductive properties of Drosophila wingless protein in Xenopus oocytes and embryos.
1992,
Pubmed
,
Xenbase
Chant,
Generation of cell polarity in yeast.
1996,
Pubmed
Chou,
Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila.
1992,
Pubmed
Collier,
Drosophila tissue polarity requires the cell-autonomous activity of the fuzzy gene, which encodes a novel transmembrane protein.
1997,
Pubmed
Couso,
Notch is required for wingless signaling in the epidermis of Drosophila.
1994,
Pubmed
Eaton,
CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium.
1995,
Pubmed
Eaton,
Planar polarization of Drosophila and vertebrate epithelia.
1997,
Pubmed
Eaton,
Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila.
1996,
Pubmed
Gubb,
Genes controlling cellular polarity in Drosophila.
1993,
Pubmed
Hays,
Wingless signaling generates pattern through two distinct mechanisms.
1997,
Pubmed
He,
A member of the Frizzled protein family mediating axis induction by Wnt-5A.
1997,
Pubmed
,
Xenbase
Kengaku,
Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud.
1998,
Pubmed
Klingensmith,
Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2.
1996,
Pubmed
,
Xenbase
Klingensmith,
The segment polarity phenotype of Drosophila involves differential tendencies toward transformation and cell death.
1989,
Pubmed
Klingensmith,
The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal.
1994,
Pubmed
Koelle,
EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins.
1996,
Pubmed
Krasnow,
A single frizzled protein has a dual function in tissue polarity.
1994,
Pubmed
Krasnow,
Dishevelled is a component of the frizzled signaling pathway in Drosophila.
1995,
Pubmed
Miller,
Signal transduction through beta-catenin and specification of cell fate during embryogenesis.
1996,
Pubmed
Moon,
Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis.
1993,
Pubmed
,
Xenbase
Moon,
WNTs modulate cell fate and behavior during vertebrate development.
1997,
Pubmed
Morais Cabral,
Crystal structure of a PDZ domain.
1996,
Pubmed
Noordermeer,
The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo.
1992,
Pubmed
Orsulic,
Cell-cell signalling: Wingless lands at last.
1996,
Pubmed
Pai,
Negative regulation of Armadillo, a Wingless effector in Drosophila.
1997,
Pubmed
Park,
The Drosophila tissue polarity gene inturned acts cell autonomously and encodes a novel protein.
1996,
Pubmed
Park,
The frizzled gene of Drosophila encodes a membrane protein with an odd number of transmembrane domains.
1994,
Pubmed
Peifer,
The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation.
1991,
Pubmed
Perrimon,
Multiple functions of segment polarity genes in Drosophila.
1987,
Pubmed
Ponting,
PDZ domains: targeting signalling molecules to sub-membranous sites.
1997,
Pubmed
Ponting,
Pleckstrin's repeat performance: a novel domain in G-protein signaling?
1996,
Pubmed
Robertson,
A stable genomic source of P element transposase in Drosophila melanogaster.
1988,
Pubmed
Rocheleau,
Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos.
1997,
Pubmed
Semënov,
Human dishevelled genes constitute a DHR-containing multigene family.
1997,
Pubmed
Shulman,
Frizzled signaling and the developmental control of cell polarity.
1998,
Pubmed
,
Xenbase
Siegfried,
Components of wingless signalling in Drosophila.
1994,
Pubmed
Slusarski,
Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A.
1997,
Pubmed
Slusarski,
Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling.
1997,
Pubmed
,
Xenbase
Sokol,
Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled.
1995,
Pubmed
,
Xenbase
Steitz,
Wnt-mediated relocalization of dishevelled proteins.
1996,
Pubmed
Strutt,
The role of RhoA in tissue polarity and Frizzled signalling.
1997,
Pubmed
Sussman,
Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled.
1994,
Pubmed
Theisen,
dishevelled is required during wingless signaling to establish both cell polarity and cell identity.
1994,
Pubmed
Thorpe,
Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm.
1997,
Pubmed
Thummel,
Vectors for Drosophila P-element-mediated transformation and tissue culture transfection.
1988,
Pubmed
Tomlinson,
Linking Frizzled and Wnt signaling in Drosophila development.
1997,
Pubmed
Torres,
Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.
1996,
Pubmed
,
Xenbase
Tsang,
Isolation and characterization of mouse dishevelled-3.
1996,
Pubmed
Vinson,
A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains.
1989,
Pubmed
Wong,
Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells.
1993,
Pubmed
Wong,
Differential transformation of mammary epithelial cells by Wnt genes.
1994,
Pubmed
Xu,
Analysis of genetic mosaics in developing and adult Drosophila tissues.
1993,
Pubmed
Yanagawa,
The dishevelled protein is modified by wingless signaling in Drosophila.
1995,
Pubmed
Yang-Snyder,
A frizzled homolog functions in a vertebrate Wnt signaling pathway.
1996,
Pubmed
,
Xenbase
Zeng,
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
1997,
Pubmed
,
Xenbase
Zwaal,
G proteins are required for spatial orientation of early cell cleavages in C. elegans embryos.
1996,
Pubmed