Publications (70) View all
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Article: Frizzled-7 signalling controls tissue separation during Xenopus gastrulation.
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ABSTRACT: Cell signalling through Frizzled receptors has evolved to considerable complexity within the metazoans. The Frizzled-dependent signalling cascade comprises several branches, whose differential activation depends on specific Wnt ligands, Frizzled receptor isoforms and the cellular context. In Xenopus laevis embryos, the canonical beta-catenin pathway contributes to the establishment of the dorsal-ventral axis. A different branch, referred to as the planar cell polarity pathway, is essential for cell polarization during elongation of the axial mesoderm by convergent extension. Here we demonstrate that a third branch of the cascade is independent of Dishevelled function and involves signalling through trimeric G proteins and protein kinase C (PKC). During gastrulation, Frizzled-7 (Fz7)-dependent PKC signalling controls cell-sorting behaviour in the mesoderm. Loss of zygotic Fz7 function results in the inability of involuted anterior mesoderm to separate from the ectoderm, which leads to severe gastrulation defects. This result provides a developmentally relevant in vivo function for the Fz/PKC pathway in vertebrates.Nature 11/2001; 413(6858):856-60. · 36.28 Impact Factor -
Article: Differential gene expression of Xenopus Pitx1, Pitx2b and Pitx2c during cement gland, stomodeum and pituitary development.
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ABSTRACT: The members of the Pitx family of homeobox transcription factors have been involved in many aspects of vertebrate embryogenesis, like for example, development of teeth, eyes and limbs. We previously reported expression patterns and function of Pitx2c in the generation of laterality and asymmetric morphogenesis of heart and gastro-intestinal tract in mouse, frog and zebrafish (Development 126 (1999) 1225; Mech. Dev. 90 (2000) 41). Here we describe the differential expression of Pitx1, Pitx2b and Pitx2c during anterior ectodermal pattern formation and differentiation of cement gland, stomodeum and pituitary in the frog Xenopus laevis.Mechanisms of Development 10/2001; 107(1-2):191-4. · 2.83 Impact Factor -
Article: Pitx1 and Pitx2c are required for ectopic cement gland formation in Xenopus laevis.
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ABSTRACT: The mucus secreting cement gland is the anterior-most ectodermal organ of the Xenopus embryo. The homeobox genes Pltx1 and Pitx2c are expressed in the cement gland primordium. Misexpression of both genes induced ectopic cement gland tissue in whole embryos and transcription of the marker genes Xag1 and Xag2 in animal cap explant cultures. Antisense morpholino oligonucleotides against Pitx1 and Pitx2c inhibited ectopic cement gland formation induced by otx2. Gene knock downs generated by morpholino oligonucleotides were specific and could be rescued by coinjection of Pitx mRNAs. These data demonstrate for the first time the requirement of specific genes for cement gland formation by loss-of-function experiments. genesis 30:144--148, 2001.genesis 08/2001; 30(3):144-8. · 2.53 Impact Factor -
Article: Functional analysis of the Xenopus frizzled 7 protein domains using chimeric receptors.
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ABSTRACT: Seven-transmembrane receptors of the frizzled family can interact with secreted Wnt ligands and transmit Wnt signals into the cell. Dependent on the ligand receptor combination, distinct Wnt pathways are activated. Xenopus frizzled 7 (Xfz7) and Xwnt-8b as well as Human frizzled 5 (Hfz5) and Xwnt-5a can act synergistically in the activation of Wnt/beta-catenin target genes siamois (Xsia) and nodal related 3 (Xnr3) and in the induction of ectopic axes in Xenopus embryos. In order to characterize the role of different protein domains of Xfz7 in Wnt/beta-catenin signaling, chimeric Xfz7/Hfz5 receptors were generated in which the extracellular (N5-TC7) or the intracellular domains (NT7-C5) between Xfz7 and Hfz5 were exchanged. We present evidence that the extracellular domain of Xfz7 can interact with Xwnt-5a and that the intracellular C-terminus can transmit a Wnt/beta-catenin signal. Despite these abilities, Xfz7 and Xwnt-5a do not act synergistically in the activation of Wnt/beta-catenin targets. This implies that the interaction of a frizzled receptor with different ligands can result in distinct cellular responses.The International Journal of Developmental Biology 02/2001; 45(1):259-64. · 2.82 Impact Factor -
Article: Interaction of Frizzled 7 and Dishevelled in Xenopus.
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ABSTRACT: Frizzled proteins act as putative Wnt receptors and depending on Wnt/Frizzled interactions distinct intracellular pathways can be activated. The canonical Wnt pathway, triggered by Wnt-1-type ligands, is the best characterized and involves the activation of the cytoplasmic protein Dishevelled (Dsh). The Xenopus frizzled 7 receptor (Xfz7) can act in the canonical (Wnt-1-type) as well as in a non-canonical Wnt pathway which involves the activation of protein kinase C (PKC). In order to analyze the interaction between Xfz7 and Xdsh protein, we tested the effect of overexpression of Xfz7 on the subcellular distribution of Xdsh-myc protein. We demonstrate that Xfz7 can recruit Xdsh-myc to the plasma membrane and target genes of the Wnt-1-type pathway such as siamois and nodal related 3 (Xnr-3) are only activated in the presence of exogenous Xdsh-myc. Xfz7 in combination with Xwnt-8b, however, is able to induce siamois even in the absence of Xdsh-myc. Similar results were obtained after expression of Human frizzled 5 (Hfz5) together with Xwnt-5a but this receptor-ligand combination recruits Xdsh-myc only very poorly to the membrane. These results suggests that the endogenous Xdsh pool and exogenous Xdsh-myc differ in their ability to be recruited by Frizzled receptors.Developmental Dynamics 09/2000; 218(4):671-80. · 2.54 Impact Factor
