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Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity.

Westfall TA, Brimeyer R, Twedt J, Gladon J, Olberding A, Furutani-Seiki M, Slusarski DC - J. Cell Biol. (2003)

Bottom Line: We describe genetic interaction between two Wnt/Ca2+ members, Wnt-5 (pipetail) and Wnt-11 (silberblick), and a reduction of Ca2+ release in Wnt-5/pipetail.The dorsalized phenotypes result from increased beta-catenin accumulation and activation of downstream genes.The Wnt-5 loss-of-function defect is consistent with Ca2+ modulation having an antagonistic interaction with Wnt/beta-catenin signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA.

ABSTRACT
We provide genetic evidence defining a role for noncanonical Wnt function in vertebrate axis formation. In zebrafish, misexpression of Wnt-4, -5, and -11 stimulates calcium (Ca2+) release, defining the Wnt/Ca2+ class. We describe genetic interaction between two Wnt/Ca2+ members, Wnt-5 (pipetail) and Wnt-11 (silberblick), and a reduction of Ca2+ release in Wnt-5/pipetail. Embryos genetically depleted of both maternal and zygotic Wnt-5 product exhibit cell movement defects as well as hyperdorsalization and axis-duplication phenotypes. The dorsalized phenotypes result from increased beta-catenin accumulation and activation of downstream genes. The Wnt-5 loss-of-function defect is consistent with Ca2+ modulation having an antagonistic interaction with Wnt/beta-catenin signaling.

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Wnt signaling network. Schematic of the stimulation of (A) canonical Wnt and (B) non-canonical Wnt/Ca2+ and planar cell polarity signaling pathways. (Note: only a few of the known components are outlined.)
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fig8: Wnt signaling network. Schematic of the stimulation of (A) canonical Wnt and (B) non-canonical Wnt/Ca2+ and planar cell polarity signaling pathways. (Note: only a few of the known components are outlined.)

Mentions: Wnt-5 loss-of-function mimics activation of Wnt/β-catenin signaling most likely by relieving negative regulation of some component(s) of the Wnt–β-catenin pathway (Fig. 8). We observe an accumulation of β-catenin protein and ectopic activation of target genes. Although further studies in the mz-ppt embryos are needed to confirm if the impact on β-catenin and target genes is a direct effect of Wnt-5/Ca2+ activity, antagonism of β-catenin levels is consistent with Wnt-5 misexpression resulting in reduced chordin expression domains. As there has not been a clear demonstration of a maternally provided canonical Wnt, the level of antagonism may lie within the cell. Recent demonstration of dsh activating Wnt/Ca2+ provides one candidate for maternal influence (Sheldahl et al., 2003). The cellular response to Ca2+ release most likely involves a network of proteins activating multiple components. Data suggests an antagonistic role for CaMKII, interfering with Xenopus gastrulation movements (Kuhl et al., 2001) and by CaMKII-dependent activation of a β-catenin/Tcf inhibiting nemolink kinase (Ishitani et al., 2003). The partial rescue of the ppt−/− phenotype suggests that although CaMKII is a downstream responder to Wnt/Ca2+ activation, other Ca2+-sensitive components may also be required. In particular, PKC (Kuhl et al., 2001) and naked cuticle (Zeng et al., 2000; Yan et al., 2001) proteins, which could lead to β-catenin accumulation or those that could influence β-catenin nuclear import (Tolwinski et al., 2003), are perhaps required.


Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity.

Westfall TA, Brimeyer R, Twedt J, Gladon J, Olberding A, Furutani-Seiki M, Slusarski DC - J. Cell Biol. (2003)

Wnt signaling network. Schematic of the stimulation of (A) canonical Wnt and (B) non-canonical Wnt/Ca2+ and planar cell polarity signaling pathways. (Note: only a few of the known components are outlined.)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172822&req=5

fig8: Wnt signaling network. Schematic of the stimulation of (A) canonical Wnt and (B) non-canonical Wnt/Ca2+ and planar cell polarity signaling pathways. (Note: only a few of the known components are outlined.)
Mentions: Wnt-5 loss-of-function mimics activation of Wnt/β-catenin signaling most likely by relieving negative regulation of some component(s) of the Wnt–β-catenin pathway (Fig. 8). We observe an accumulation of β-catenin protein and ectopic activation of target genes. Although further studies in the mz-ppt embryos are needed to confirm if the impact on β-catenin and target genes is a direct effect of Wnt-5/Ca2+ activity, antagonism of β-catenin levels is consistent with Wnt-5 misexpression resulting in reduced chordin expression domains. As there has not been a clear demonstration of a maternally provided canonical Wnt, the level of antagonism may lie within the cell. Recent demonstration of dsh activating Wnt/Ca2+ provides one candidate for maternal influence (Sheldahl et al., 2003). The cellular response to Ca2+ release most likely involves a network of proteins activating multiple components. Data suggests an antagonistic role for CaMKII, interfering with Xenopus gastrulation movements (Kuhl et al., 2001) and by CaMKII-dependent activation of a β-catenin/Tcf inhibiting nemolink kinase (Ishitani et al., 2003). The partial rescue of the ppt−/− phenotype suggests that although CaMKII is a downstream responder to Wnt/Ca2+ activation, other Ca2+-sensitive components may also be required. In particular, PKC (Kuhl et al., 2001) and naked cuticle (Zeng et al., 2000; Yan et al., 2001) proteins, which could lead to β-catenin accumulation or those that could influence β-catenin nuclear import (Tolwinski et al., 2003), are perhaps required.

Bottom Line: We describe genetic interaction between two Wnt/Ca2+ members, Wnt-5 (pipetail) and Wnt-11 (silberblick), and a reduction of Ca2+ release in Wnt-5/pipetail.The dorsalized phenotypes result from increased beta-catenin accumulation and activation of downstream genes.The Wnt-5 loss-of-function defect is consistent with Ca2+ modulation having an antagonistic interaction with Wnt/beta-catenin signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA.

ABSTRACT
We provide genetic evidence defining a role for noncanonical Wnt function in vertebrate axis formation. In zebrafish, misexpression of Wnt-4, -5, and -11 stimulates calcium (Ca2+) release, defining the Wnt/Ca2+ class. We describe genetic interaction between two Wnt/Ca2+ members, Wnt-5 (pipetail) and Wnt-11 (silberblick), and a reduction of Ca2+ release in Wnt-5/pipetail. Embryos genetically depleted of both maternal and zygotic Wnt-5 product exhibit cell movement defects as well as hyperdorsalization and axis-duplication phenotypes. The dorsalized phenotypes result from increased beta-catenin accumulation and activation of downstream genes. The Wnt-5 loss-of-function defect is consistent with Ca2+ modulation having an antagonistic interaction with Wnt/beta-catenin signaling.

Show MeSH