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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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Morphological phenotypes in Wnt-5/ppt and Ca2+- inhibited embryos. Lateral view, anterior to the right of 24–36 hpf embryos. (A) In wild-type, the block arrow indicates one eye, the other is out of the focal plane and the dashed lined demarcates the tail extending posteriorly off the yolk. (B) The Wnt-11 mutant (slb−/−) embryo has a fused eye, the arrow indicates the lens. (C) In Wnt-5 mutant (ppt−/−), the dashed arrow demarcates the shortened-curled tail defect and in the (D) double mutant (slb−/−; ppt−/−), the block arrow indicates the fused eye, whereas the dashed arrow marks the shortened-twisted tail. The notochord and one set of somites are highlighted by a dashed line in (E) IP3R-inhibited (XeC), and (F) ppt−/− embryos. The presence of a protruding yolk is an indication of incomplete epiboly cell movements. Fused eyes and shortened twisted trunks can also be observed in (G) Ca2+-inhibited (L-690,330-treated) embryos.
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fig3: Morphological phenotypes in Wnt-5/ppt and Ca2+- inhibited embryos. Lateral view, anterior to the right of 24–36 hpf embryos. (A) In wild-type, the block arrow indicates one eye, the other is out of the focal plane and the dashed lined demarcates the tail extending posteriorly off the yolk. (B) The Wnt-11 mutant (slb−/−) embryo has a fused eye, the arrow indicates the lens. (C) In Wnt-5 mutant (ppt−/−), the dashed arrow demarcates the shortened-curled tail defect and in the (D) double mutant (slb−/−; ppt−/−), the block arrow indicates the fused eye, whereas the dashed arrow marks the shortened-twisted tail. The notochord and one set of somites are highlighted by a dashed line in (E) IP3R-inhibited (XeC), and (F) ppt−/− embryos. The presence of a protruding yolk is an indication of incomplete epiboly cell movements. Fused eyes and shortened twisted trunks can also be observed in (G) Ca2+-inhibited (L-690,330-treated) embryos.

Mentions: The slb mutation affects forebrain patterning and homozygous slbtz216 mutant embryos often have incomplete separation of the eyes (Fig. 3 B, arrow pointing to a fused lens) compared with wild-type (Fig. 3 A). Homozygous pptti265 mutant embryos display shortened body length and undulating notochords but most commonly tail defects (deformed tip of tail resembling a pipe; Fig. 3 C, arrow). To test for genetic interaction, we generated adult fish doubly heterozygous for pptti265 and slbtz216 and crossed to obtain doubly homozygous mutant embryos, confirmed by PCR of genomic DNA. The double homozygous mutant embryo phenotype is markedly more severe than the additive of the single mutant combinations. The eye anlagen fuse more frequently in the double mutant embryos than in slb−/− embryos (Fig. 3 D). Double homozygous mutant embryos also have more severe tail and trunk defects than observed in ppt−/− (Fig. 3 D).


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)

Morphological phenotypes in Wnt-5/ppt and Ca2+- inhibited embryos. Lateral view, anterior to the right of 24–36 hpf embryos. (A) In wild-type, the block arrow indicates one eye, the other is out of the focal plane and the dashed lined demarcates the tail extending posteriorly off the yolk. (B) The Wnt-11 mutant (slb−/−) embryo has a fused eye, the arrow indicates the lens. (C) In Wnt-5 mutant (ppt−/−), the dashed arrow demarcates the shortened-curled tail defect and in the (D) double mutant (slb−/−; ppt−/−), the block arrow indicates the fused eye, whereas the dashed arrow marks the shortened-twisted tail. The notochord and one set of somites are highlighted by a dashed line in (E) IP3R-inhibited (XeC), and (F) ppt−/− embryos. The presence of a protruding yolk is an indication of incomplete epiboly cell movements. Fused eyes and shortened twisted trunks can also be observed in (G) Ca2+-inhibited (L-690,330-treated) embryos.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Morphological phenotypes in Wnt-5/ppt and Ca2+- inhibited embryos. Lateral view, anterior to the right of 24–36 hpf embryos. (A) In wild-type, the block arrow indicates one eye, the other is out of the focal plane and the dashed lined demarcates the tail extending posteriorly off the yolk. (B) The Wnt-11 mutant (slb−/−) embryo has a fused eye, the arrow indicates the lens. (C) In Wnt-5 mutant (ppt−/−), the dashed arrow demarcates the shortened-curled tail defect and in the (D) double mutant (slb−/−; ppt−/−), the block arrow indicates the fused eye, whereas the dashed arrow marks the shortened-twisted tail. The notochord and one set of somites are highlighted by a dashed line in (E) IP3R-inhibited (XeC), and (F) ppt−/− embryos. The presence of a protruding yolk is an indication of incomplete epiboly cell movements. Fused eyes and shortened twisted trunks can also be observed in (G) Ca2+-inhibited (L-690,330-treated) embryos.
Mentions: The slb mutation affects forebrain patterning and homozygous slbtz216 mutant embryos often have incomplete separation of the eyes (Fig. 3 B, arrow pointing to a fused lens) compared with wild-type (Fig. 3 A). Homozygous pptti265 mutant embryos display shortened body length and undulating notochords but most commonly tail defects (deformed tip of tail resembling a pipe; Fig. 3 C, arrow). To test for genetic interaction, we generated adult fish doubly heterozygous for pptti265 and slbtz216 and crossed to obtain doubly homozygous mutant embryos, confirmed by PCR of genomic DNA. The double homozygous mutant embryo phenotype is markedly more severe than the additive of the single mutant combinations. The eye anlagen fuse more frequently in the double mutant embryos than in slb−/− embryos (Fig. 3 D). Double homozygous mutant embryos also have more severe tail and trunk defects than observed in ppt−/− (Fig. 3 D).

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