Morpholino phenocopies of the swirl, snailhouse, somitabun, minifin, silberblick, and pipetail mutations

Lele, Zsolt; Bakkers, Jeroen; Hammerschmidt, Matthias

doi:10.1002/gene.1063

Cited by 100 publications

(97 citation statements)

References 25 publications

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“…It has previously been reported that Wnt5a͞pipetail and Wnt11͞silberblick are the ligands of the noncanonical Wnt signaling pathway that control CE in zebrafish embryogenesis (8)(9)(10)27). We found that mRNAs encoding full-size mouse Diversin or the ankyrin repeats rescued CE phenotypes induced by Wnt11͞5a MO (Fig.…”

Section: Resultssupporting

confidence: 54%

Diversin regulates heart formation and gastrulation movements in development

Moeller

Jenny

Schaeffer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Canonical and noncanonical Wnt signaling regulate crucial events in the development of vertebrates and invertebrates. In this work we show that vertebrate Diversin, a potential orthologue of Drosophila Diego, controls fusion of heart precursors and gastrulation movements in zebrafish embryogenesis. These events are regulated by noncanonical Wnt signaling, which is independent of ␤-catenin. We found that Diversin directly interacts with Dishevelled and that this interaction is necessary and sufficient to mediate signals of the noncanonical Wnt pathway to downstream effectors like Rho family GTPases and Jun N-terminal kinase. The ankyrin repeats of Diversin are required for the interaction with Dishevelled, for the activation of noncanonical Wnt signaling, and for the biological responses. The mutation K446M in the DEP domain of vertebrate Dishevelled, which mimics a classical Drosophila loss of function mutation, prevents functional interaction with Diversin's ankyrin repeats. Diversin also affects planar cell polarity in Drosophila, which is controlled by the noncanonical Wnt signaling pathway. Our data thus demonstrate that Diversin and Dishevelled function together in a mutually dependent fashion in zebrafish gastrulation and organ formation.convergence and extension ͉ Dishevelled ͉ embryogenesis ͉ noncanonical Wnt signaling ͉ Rho family GTPases

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Section: Resultssupporting

confidence: 54%

Diversin regulates heart formation and gastrulation movements in development

Moeller

Jenny

Schaeffer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, we designed 5-base pair mismatch MOs (5mmMO-smad1 and 5mmMO-smad5) as negative controls. Although the consequences of smad5 loss-of-function have previously been examined by analysis of mutants and anti-sense morpholino knockdowns (Hild et al, 1999;Lele et al, 2001;Kramer et al, 2002), the effects of specific loss of smad1 have yet to be reported. Both MO-smad1 and MO-smad5 resulted in a strong dorsalization phenotype at 24 hours similar to that seen in bmp mutants and in embryos treated with bmp morpholinos (Lele et al, 2001) (data not presented).…”

Section: )mentioning

confidence: 99%

“…Although the consequences of smad5 loss-of-function have previously been examined by analysis of mutants and anti-sense morpholino knockdowns (Hild et al, 1999;Lele et al, 2001;Kramer et al, 2002), the effects of specific loss of smad1 have yet to be reported. Both MO-smad1 and MO-smad5 resulted in a strong dorsalization phenotype at 24 hours similar to that seen in bmp mutants and in embryos treated with bmp morpholinos (Lele et al, 2001) (data not presented). In line with the role of Smad5 downstream of Bmp signalling, injection of MO-smad5 was sufficient to cause complete loss of the non-neural ectoderm marker gata2 at the 50% epiboly stage (Fig.…”

Section: )mentioning

confidence: 99%

A change in response to Bmp signalling precedes ectodermal fate choice

Dee

Gibson²,

Rengifo³

et al. 2007

Int. J. Dev. Biol.

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Bone morphogenetic protein (Bmp) signalling plays a central role in the decision of ectoderm to adopt either neural or non-neural fates. The effects of this signalling are seen at midgastrulation in the activation of genes such as the Gata factors and the repression of genes such as the SoxB1 transcription factors in the non-neural regions. Using zebrafish embryos, we show that this Bmp signalling does not repress the expression of these same neural markers just 2-3 hours earlier. Since expression of the Bmp signalling effector, Smad1, only begins during early gastrulation, we tested the role of Smad1 and Smad5 (which is maternally expressed) in controlling gene expression both before and during gastrulation. This showed that the absence of Smad1 does not explain the lack of response of neural genes to Bmp signalling at early stages. However, these experiments showed that expression of the non-neural marker, gata2, is mediated by Smad5 in the absence of Smad1 at early stages, but is dependent upon Smad1 at later stages. Hence, we have shown a dynamic change in the molecular machinery underlying the Bmp response in the ectoderm during gastrulation stages of development.

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“…In these experiments, genes with known loss of function phenotypes are targeted with MOs. A collection of 17 genes was arbitrarily selected and screened; 16 of these genes were effectively targeted, resulting in embryos with specific phenocopies of known mutations (Nasevicius and Ekker, 2000; Lele et al, 2001). This remarkable success rate suggests that the core mechanism of translational inhibition by MOs (Fig.…”

Section: Mo Targeting Effectiveness Limitations and Essential Controlsmentioning

confidence: 99%