DWnt4 Regulates Cell Movement and Focal Adhesion Kinase during Drosophila Ovarian Morphogenesis

Cohen, Ethan David; Mariol, Marie-Christine; Wallace, Rachel M.H.; Weyers, Jason; Kamberov, Yana G.; Pradel, Jacques; Wilder, Elizabeth L.

doi:10.1016/s1534-5807(02)00142-9

Cited by 123 publications

(144 citation statements)

References 56 publications

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“…With respect to DWnt4, we find that it binds to Fz, Dfz2, and Dfz4. This agrees with the phenotypes of DWnt4 and Dfz2 in the ovary: a cell migration defect seen for both the ligand and the receptor (55).…”

Section: Implications Of the Interactions Between Different Wnts Andsupporting

confidence: 88%

Ligand Receptor Interactions in the Wnt Signaling Pathway inDrosophila

Nusse

2002

Journal of Biological Chemistry

166

160

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Section: Implications Of the Interactions Between Different Wnts Andsupporting

confidence: 88%

Ligand Receptor Interactions in the Wnt Signaling Pathway inDrosophila

Nusse

2002

Journal of Biological Chemistry

166

160

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“…PKC activation is another recently described mechanism of Wnt-dependent cell motility, associated with the activity of Wnt-5a on melanoma cells (26), DWnt-4 on Drosophila ovarian epithelial cells (25) and convergent extension movements in Xenopus (27). These processes are thought to involve Dvl (25,27). Thus far, we have not obtained evidence of Wnt-dependent PKC activation in our CHO cell model system.…”

Section: Dvl-2 Regulates Wnt3a-dependent Motilitymentioning

confidence: 68%

“…2 We presume that extraneous factors are present in the L and perhaps also Wnt-3a CM that account for this activity and likely contribute to the motility elicited by the CM in the transwell assay. PKC activation is another recently described mechanism of Wnt-dependent cell motility, associated with the activity of Wnt-5a on melanoma cells (26), DWnt-4 on Drosophila ovarian epithelial cells (25) and convergent extension movements in Xenopus (27). These processes are thought to involve Dvl (25,27).…”

Section: Dvl-2 Regulates Wnt3a-dependent Motilitymentioning

confidence: 99%

“…Wnt-11 (Silberblick) was identified as an activator of the planar cell polarity pathway in zebrafish (15) and Xenopus (16), whereas Dvl (16 -21), RhoA/ROCK, and Rac/JNK activation (22,23) were shown to be effectors of planar cell polarity signaling and cell movement in various model systems. Although activation of all the key effectors in the Wnt/Ca 2ϩ /PKC pathway (24) has not been documented in cell motility models, there are numerous reports of Wnt-dependent, PKC activity contributing to cell migration (25)(26)(27).…”

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confidence: 99%

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Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2*[boxs]

Endo

Wolf

Muraiso

et al. 2005

Journal of Biological Chemistry

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Wnts stimulate cell migration, although the mechanisms responsible for this effect are not fully understood. To investigate the pathways that mediate Wnt-dependent cell motility, we treated Chinese hamster ovary cells with Wnt-3a-conditioned medium and monitored changes in cell shape and movement. Wnt-3a induced cell spreading, formation of protrusive structures, reorganization of stress fibers and migration. Although Wnt-3a stabilized ␤-catenin, two inhibitors of the ␤-catenin/canonical pathway, Dickkopf-1 and a dominant-negative T cell factor construct, did not reduce motility. The small GTPase RhoA also was activated by Wnt-3a. In contrast to ␤-catenin signaling, inhibition of Rho kinase partially blocked motility. Because Dishevelled (Dvl) proteins are effectors of both canonical and noncanonical Wnt signaling, we used immunofluorescent analysis and small interference RNA technology to evaluate the role of Dvl in cell motility. Specific knock-down of Dvl-2 expression markedly reduced Wnt-3a-dependent changes in cell shape and movement, suggesting that this Dvl isoform had a predominant role in mediating Wnt-3a-dependent motility in Chinese hamster ovary cells.

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“…One explanation for this may have to do with the multifunctional nature of Frizzled receptors. Genetic studies in Drosophila have shown that DFz1 and DFz2, which are developmentally redundant for canonical signaling, distinctly function in planar cell polarity (43,44) and cell motility, respectively (43,45). Because of this multifunctionality, the same Frizzled receptor may bind more than just one class of Wnt ligands.…”

Section: Discussionmentioning

confidence: 99%

Multiple Mechanisms for Wnt11-mediated Repression of the Canonical Wnt Signaling Pathway

Maye

Zheng

et al. 2004

Journal of Biological Chemistry

124

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The effect of a noncanonical Wnt, Wnt11, on canonical Wnt signaling stimulated by Wnt1 and activated forms of LRP5 (low density lipoprotein receptor-related protein-5), Dishevelled1 (Dvl1), and ␤-catenin was examined in NIH3T3 cells and P19 embryonic carcinoma cells. Wnt11 repressed Wnt1-mediated activation of LEF-1 reporter activity in both cell lines. However, Wnt11 was unable to inhibit canonical signaling activated by LRP5, Dvl1, or ␤-catenin in NIH3T3 cells, although it could in P19 cells. In addition, Wnt11-mediated inhibition of canonical signaling in NIH3T3 cells is ligand-specific; Wnt11 could effectively repress canonical signaling activated by Wnt1, Wnt3, or Wnt3a but not by Wnt7a or Wnt7b. Coculture experiments with NIH3T3 cells showed that the co-expression of Wnt11 with Wnt1 was not an essential requirement for the inhibition, suggesting receptor competition as a possible mechanism. Moreover, in both cell types, elevation of intracellular Ca 2؉ levels, which can result from Wnt11 treatment, led to the inhibition of canonical signaling. This result suggests that Wnt11 might not be able to signal in NIH3T3. Furthermore, P19 cells were found to express both endogenous canonical Wnts and Wnt11. Knockdown of Wnt11 expression using siRNA resulted in increased LEF-1 reporter activity, thus indicating that Wnt11-mediated suppression of canonical signaling exists in vivo.The Wnt gene family encodes for a conserved class of secreted signaling molecules and is considered one of the major gene families essential for proper embryonic patterning and organogenesis. Genome sequencing projects have revealed that a large number of Wnt genes exist, including 7 Wnt genes in Drosophila and at least 19 Wnt genes in humans. 1 Wnt proteins function as growth factors and morphogens modulating cell growth and specifying cell fate. Early segment polarity screens in Drosophila resulted in the identification of key components of a "canonical" Wnt signaling pathway (2). Since then, extensive research on the canonical pathway has identified several genes, the gene products of which interact in a complex series of mechanisms that ultimately regulate the canonical pathway.At the cell surface, Wnt proteins activate the pathway through binding a receptor complex consisting of Frizzled, a seven transmembrane receptor, and its co-receptor LRP-5/6 2 (low density lipoprotein receptor-related protein-5/6) (3-5). Intracellular mediators of the canonical pathway include Dishevelled and ␤-catenin (6, 7), which promote pathway activation, and Axin and GSK-3␤ (8, 9), which negatively regulate the pathway. In the absence of Wnt ligand, cytoplasmic levels of ␤-catenin protein remain low, as a result of its association with GSK-3␤ and Axin, which target it for proteolytic degradation (10). Upon Wnt ligand binding, GSK-3␤ is inhibited, and cytoplasmic levels of ␤-catenin protein increase (11) and subsequently translocate into the nucleus, where it functions as a transcriptional co-activator, commonly associating with members of the LEF/TCF family...

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DWnt4 Regulates Cell Movement and Focal Adhesion Kinase during Drosophila Ovarian Morphogenesis

Cited by 123 publications

References 56 publications

Ligand Receptor Interactions in the Wnt Signaling Pathway inDrosophila

Ligand Receptor Interactions in the Wnt Signaling Pathway inDrosophila

Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2*[boxs]

Multiple Mechanisms for Wnt11-mediated Repression of the Canonical Wnt Signaling Pathway

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