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Doris Wedlich - One of the best experts on this subject based on the ideXlab platform.
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Antagonistic regulation of Convergent Extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca2+ signaling.
Mechanisms of development, 2020Co-Authors: Michael Kuhl, Karin Geis, Laird C Sheldahl, T Pukrop, Randall T Moon, Doris WedlichAbstract:Convergent Extension movements are the main driving force of Xenopus gastrulation. A fine-tuned regulation of cadherin-mediated cell-cell adhesion is thought to be required for this process. Members of the Wnt family of extracellular glycoproteins have been shown to modulate cadherin-mediated cell-cell adhesion, Convergent Extension movements, and cell differentiation. Here we show that endogenous Wnt/beta-catenin signaling activity is essential for Convergent Extension movements due to its effect on gene expression rather than on cadherins. Our data also suggest that XLEF-1 rather than XTCF-3 is required for Convergent Extension movements and that XLEF-1 functions in this context in the Wnt/beta-catenin pathway to regulate Xnr-3. In contrast, activation of the Wnt/Ca2+ pathway blocks Convergent Extension movements, with potential regulation of the Wnt/beta-catenin pathway at two different levels. PKC, activated by the Wnt/Ca2+ pathway, blocks the Wnt/beta-catenin pathway upstream of beta-catenin and phosphorylates Dishevelled. CamKII, also activated by the Wnt/Ca2+ pathway, inhibits the Wnt/beta-catenin signaling cascade downstream of beta-catenin. Thus, an opposing cross-talk of two distinct Wnt signaling cascades regulates Convergent Extension movements in Xenopus.
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wnt 11 and fz7 reduce cell adhesion in Convergent Extension by sequestration of papc and c cadherin
Journal of Cell Biology, 2012Co-Authors: Bianca Kraft, Herbert Steinbeisser, Corinna D Berger, Veronika Wallkamm, Doris WedlichAbstract:Wnt-11/planar cell polarity signaling polarizes mesodermal cells undergoing Convergent Extension during Xenopus laevis gastrulation. These shape changes associated with lateral intercalation behavior require a dynamic modulation of cell adhesion. In this paper, we report that Wnt-11/frizzled-7 (Fz7) controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin (PAPC; denoted as AMCP) and C-cadherin (denoted as AMCC) via distinct Fz7 interaction domains. When PAPC was part of a Wnt-11–Fz7 complex, its Dynamin1- and clathrin-dependent internalization was blocked. This membrane stabilization of AMCP (Fz7/PAPC) by Wnt-11 prevented C-cadherin clustering, resulting in reduced cell adhesion and modified cell sorting activity. Importantly, Wnt-11 did not influence C-cadherin internalization; instead, it promoted the formation of AMCC (Fz7/Cadherin), which competed with cis-dimerization of C-cadherin. Because PAPC and C-cadherin did not directly interact and did not form a joint complex with Fz7, we suggest that Wnt-11 triggers the formation of two distinct complexes, AMCC and AMCP, that act in parallel to reduce cell adhesion by hampering lateral clustering of C-cadherin.
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paraxial protocadherin coordinates cell polarity during Convergent Extension via rho a and jnk
The EMBO Journal, 2004Co-Authors: Frank Unterseher, Doris Wedlich, Joerg A Hefele, Klaudia Giehl, Eddy M De Robertis, Alexandra SchambonyAbstract:Convergent Extension movements occur ubiquitously in animal development. This special type of cell movement is controlled by the Wnt/planar cell polarity (PCP) pathway. Here we show that Xenopus paraxial protocadherin (XPAPC) functionally interacts with the Wnt/PCP pathway in the control of convergence and Extension (CE) movements in Xenopus laevis. XPAPC functions as a signalling molecule that coordinates cell polarity of the involuting mesoderm in mediolateral orientation and thus selectively promotes convergence in CE movements. XPAPC signals through the small GTPases Rho A and Rac 1 and c-jun N-terminal kinase (JNK). Loss of XPAPC function blocks Rho A-mediated JNK activation. Despite common downstream components, XPAPC and Wnt/PCP signalling are not redundant, and the activity of both, XPAPC and PCP signalling, is required to coordinate CE movements.
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antagonistic regulation of Convergent Extension movements in xenopus by wnt β catenin and wnt ca2 signaling
Mechanisms of Development, 2001Co-Authors: Michael Kuhl, Karin Geis, Laird C Sheldahl, T Pukrop, Randall T Moon, Doris WedlichAbstract:Convergent Extension movements are the main driving force of Xenopus gastrulation. A fine-tuned regulation of cadherin-mediated cell–cell adhesion is thought to be required for this process. Members of the Wnt family of extracellular glycoproteins have been shown to modulate cadherin-mediated cell–cell adhesion, Convergent Extension movements, and cell differentiation. Here we show that endogenous Wnt/β-catenin signaling activity is essential for Convergent Extension movements due to its effect on gene expression rather than on cadherins. Our data also suggest that XLEF-1 rather than XTCF-3 is required for Convergent Extension movements and that XLEF-1 functions in this context in the Wnt/β-catenin pathway to regulate Xnr-3. In contrast, activation of the Wnt/Ca2+ pathway blocks Convergent Extension movements, with potential regulation of the Wnt/β-catenin pathway at two different levels. PKC, activated by the Wnt/Ca2+ pathway, blocks the Wnt/β-catenin pathway upstream of β-catenin and phosphorylates Dishevelled. CamKII, also activated by the Wnt/Ca2+ pathway, inhibits the Wnt/β-catenin signaling cascade downstream of β-catenin. Thus, an opposing cross-talk of two distinct Wnt signaling cascades regulates Convergent Extension movements in Xenopus.
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Antagonistic regulation of Convergent Extension movements in Xenopus by Wnt/β-catenin and Wnt/Ca2+ signaling
Mechanisms of Development, 2001Co-Authors: Michael Kuhl, Karin Geis, Laird C Sheldahl, T Pukrop, Randall T Moon, Doris WedlichAbstract:Convergent Extension movements are the main driving force of Xenopus gastrulation. A fine-tuned regulation of cadherin-mediated cell–cell adhesion is thought to be required for this process. Members of the Wnt family of extracellular glycoproteins have been shown to modulate cadherin-mediated cell–cell adhesion, Convergent Extension movements, and cell differentiation. Here we show that endogenous Wnt/β-catenin signaling activity is essential for Convergent Extension movements due to its effect on gene expression rather than on cadherins. Our data also suggest that XLEF-1 rather than XTCF-3 is required for Convergent Extension movements and that XLEF-1 functions in this context in the Wnt/β-catenin pathway to regulate Xnr-3. In contrast, activation of the Wnt/Ca2+ pathway blocks Convergent Extension movements, with potential regulation of the Wnt/β-catenin pathway at two different levels. PKC, activated by the Wnt/Ca2+ pathway, blocks the Wnt/β-catenin pathway upstream of β-catenin and phosphorylates Dishevelled. CamKII, also activated by the Wnt/Ca2+ pathway, inhibits the Wnt/β-catenin signaling cascade downstream of β-catenin. Thus, an opposing cross-talk of two distinct Wnt signaling cascades regulates Convergent Extension movements in Xenopus.
Suncheol Choi - One of the best experts on this subject based on the ideXlab platform.
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β arrestin 1 mediates non canonical wnt pathway to regulate Convergent Extension movements
Biochemical and Biophysical Research Communications, 2013Co-Authors: Edmond Changkyun Park, Hyejeong Na, Suncheol ChoiAbstract:Abstract β-Arrestins are multifaceted proteins that play critical roles in termination of G protein-coupled receptor (GPCR) signaling by inducing its desensitization and internalization as well as in facilitation of many intracellular signaling pathways. Here, we examine using Xenopus embryos whether β-arrestin 1 might act as a mediator of β-catenin-independent Wnt (non-canonical) signaling. Xenopus β-arrestin 1 (xβarr1) is expressed in the tissues undergoing extensive cell rearrangements in early development. Gain- and loss-of-function analyses of xβarr1 revealed that it regulates Convergent Extension (CE) movements of mesodermal tissue with no effect on cell fate specification. In addition, rescue experiments showed that xβarr1 controls CE movements downstream of Wnt11/Fz7 signal and via activation of RhoA and JNK. In line with this, xβarr1 associated with key Wnt components including Ryk, Fz, and Dishevelled. Furthermore, we found that xβarr1 could recover CE movements inhibited by xβarr2 knockdown or its endocytosis defective mutant. Overall, these results suggest that β-arrestin 1 and 2 share interchangeable endocytic activity to regulate CE movements downstream of the non-canonical Wnt pathway.
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xenopus cdc42 regulates Convergent Extension movements during gastrulation through wnt ca2 signaling pathway
Developmental Biology, 2002Co-Authors: Suncheol ChoiAbstract:Abstract Rho GTPases are molecular switches that regulate many essential cellular processes, including actin dynamics, cell adhesion, cell-cycle progression, and transcription. We have isolated the Xenopus homolog of Rho GTPase Cdc42 and examined its potential role during gastrulation movements in early Xenopus embryos. XCdc42 is expressed in tissues undergoing extensive morphogenetic changes, such as the deep layers of involuting mesoderm and posterior neuroectoderm during gastrulation, and somitic mesoderm at neurula stages. Overexpression of either wild-type (WT) or dominant-negative (DN) XCdc42 interferes with Convergent Extension movements in intact embryos, activin-stimulated animal caps, and dorsal marginal zone explants. These effects occur without affecting mesodermal specification. Overexpression of WT or DN XCdc42 leads to the decrease and increase of cell adhesiveness of blastomeres, respectively, as demonstrated by the cell adhesion assay. In addition, when overexpressed, PKC-α, XWnt-5a, and Mfz-3 inhibit activin-induced Convergent Extension in animal cap explants. This inhibition can be rescued by coexpression of DN XCdc42, implying that XCdc42 acts downstream of the Wnt/Ca2+ signaling pathway involving PKC activation. XCdc42 also lies downstream of XWnt-5a in the regulation of Ca2+-dependent cell adhesion. Taken together, our results suggest that XCdc42 plays a role in the regulation of Convergent Extension movements during gastrulation through the protein kinase C-mediated Wnt/Ca2+ pathway.
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Xenopus Cdc42 regulates Convergent Extension movements during gastrulation through Wnt/Ca2+ signaling pathway.
Developmental Biology, 2002Co-Authors: Suncheol ChoiAbstract:Abstract Rho GTPases are molecular switches that regulate many essential cellular processes, including actin dynamics, cell adhesion, cell-cycle progression, and transcription. We have isolated the Xenopus homolog of Rho GTPase Cdc42 and examined its potential role during gastrulation movements in early Xenopus embryos. XCdc42 is expressed in tissues undergoing extensive morphogenetic changes, such as the deep layers of involuting mesoderm and posterior neuroectoderm during gastrulation, and somitic mesoderm at neurula stages. Overexpression of either wild-type (WT) or dominant-negative (DN) XCdc42 interferes with Convergent Extension movements in intact embryos, activin-stimulated animal caps, and dorsal marginal zone explants. These effects occur without affecting mesodermal specification. Overexpression of WT or DN XCdc42 leads to the decrease and increase of cell adhesiveness of blastomeres, respectively, as demonstrated by the cell adhesion assay. In addition, when overexpressed, PKC-α, XWnt-5a, and Mfz-3 inhibit activin-induced Convergent Extension in animal cap explants. This inhibition can be rescued by coexpression of DN XCdc42, implying that XCdc42 acts downstream of the Wnt/Ca2+ signaling pathway involving PKC activation. XCdc42 also lies downstream of XWnt-5a in the regulation of Ca2+-dependent cell adhesion. Taken together, our results suggest that XCdc42 plays a role in the regulation of Convergent Extension movements during gastrulation through the protein kinase C-mediated Wnt/Ca2+ pathway.
Masazumi Tada - One of the best experts on this subject based on the ideXlab platform.
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Convergent Extension using collective cell migration and cell intercalation to shape embryos
Development, 2012Co-Authors: Masazumi Tada, Carlphilipp HeisenbergAbstract:Body axis elongation represents a common and fundamental morphogenetic process in development. A key mechanism triggering body axis elongation without additional growth is Convergent Extension (CE), whereby a tissue undergoes simultaneous narrowing and Extension. Both collective cell migration and cell intercalation are thought to drive CE and are used to different degrees in various species as they elongate their body axis. Here, we provide an overview of CE as a general strategy for body axis elongation and discuss conserved and divergent mechanisms underlying CE among different species.
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role of glypican 4 in the regulation of Convergent Extension movements during gastrulation in xenopus laevis
Development, 2003Co-Authors: Bisei Ohkawara, Takamasa S Yamamoto, Masazumi Tada, Naoto UenoAbstract:Coordinated morphogenetic cell movements during gastrulation are crucial for establishing embryonic axes in animals. Most recently, the non-canonical Wnt signaling cascade (PCP pathway) has been shown to regulate Convergent Extension movements in Xenopus and zebrafish. Heparan sulfate proteoglycans (HSPGs) are known as modulators of intercellular signaling, and are required for gastrulation movements in vertebrates. However, the function of HSPGs is poorly understood. We analyze the function of Xenopus glypican 4 (Xgly4), which is a member of membrane-associated HSPG family. In situ hybridization revealed that Xgly4 is expressed in the dorsal mesoderm and ectoderm during gastrulation. Reducing the levels of Xgly4 inhibits cell-membrane accumulation of Dishevelled (Dsh), which is a transducer of the Wnt signaling cascade, and thereby disturbs cell movements during gastrulation. Rescue analysis with different Dsh mutants and Wnt11 demonstrated that Xgly4 functions in the non-canonical Wnt/PCP pathway, but not in the canonical Wnt/β-catenin pathway, to regulate gastrulation movements. We also provide evidence that the Xgly4 protein physically binds Wnt ligands. Therefore, our results suggest that Xgly4 functions as positive regulator in non-canonical Wnt/PCP signaling during gastrulation.
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silberblick wnt11 mediates Convergent Extension movements during zebrafish gastrulation
Nature, 2000Co-Authors: Carlphilipp Heisenberg, Masazumi Tada, Gerdjorg Rauch, Leonor Saude, Miguel L Concha, Robert Geisler, Derek L Stemple, J C Smith, Stephen W WilsonAbstract:Vertebrate gastrulation involves the specification and coordinated movement of large populations of cells that give rise to the ectodermal, mesodermal and endodermal germ layers. Although many of the genes involved in the specification of cell identity during this process have been identified, little is known of the genes that coordinate cell movement. Here we show that the zebrafish silberblick (slb) locus1 encodes Wnt11 and that Slb/Wnt11 activity is required for cells to undergo correct Convergent Extension movements during gastrulation. In the absence of Slb/Wnt11 function, abnormal Extension of axial tissue results in cyclopia and other midline defects in the head2. The requirement for Slb/Wnt11 is cell non-autonomous, and our results indicate that the correct Extension of axial tissue is at least partly dependent on medio-lateral cell intercalation in paraxial tissue. We also show that the slb phenotype is rescued by a truncated form of Dishevelled that does not signal through the canonical Wnt pathway3, suggesting that, as in flies4, Wnt signalling might mediate morphogenetic events through a divergent signal transduction cascade. Our results provide genetic and experimental evidence that Wnt activity in lateral tissues has a crucial role in driving the Convergent Extension movements underlying vertebrate gastrulation.
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Silberblick/Wnt11 mediates Convergent Extension movements during zebrafish gastrulation.
Nature, 2000Co-Authors: Carlphilipp Heisenberg, Masazumi Tada, Gerdjorg Rauch, Leonor Saude, Miguel L Concha, Robert Geisler, Derek L Stemple, J C Smith, Stephen W WilsonAbstract:Vertebrate gastrulation involves the specification and coordinated movement of large populations of cells that give rise to the ectodermal, mesodermal and endodermal germ layers. Although many of the genes involved in the specification of cell identity during this process have been identified, little is known of the genes that coordinate cell movement. Here we show that the zebrafish silberblick (slb) locus1 encodes Wnt11 and that Slb/Wnt11 activity is required for cells to undergo correct Convergent Extension movements during gastrulation. In the absence of Slb/Wnt11 function, abnormal Extension of axial tissue results in cyclopia and other midline defects in the head2. The requirement for Slb/Wnt11 is cell non-autonomous, and our results indicate that the correct Extension of axial tissue is at least partly dependent on medio-lateral cell intercalation in paraxial tissue. We also show that the slb phenotype is rescued by a truncated form of Dishevelled that does not signal through the canonical Wnt pathway3, suggesting that, as in flies4, Wnt signalling might mediate morphogenetic events through a divergent signal transduction cascade. Our results provide genetic and experimental evidence that Wnt activity in lateral tissues has a crucial role in driving the Convergent Extension movements underlying vertebrate gastrulation.
Richard M Harland - One of the best experts on this subject based on the ideXlab platform.
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roles of wnt pathway genes wls wnt9a wnt5b frzb and gpc4 in regulating Convergent Extension during zebrafish palate morphogenesis
Development, 2016Co-Authors: Lucie Rochard, Richard M Harland, Stefanie D Monica, Irving T C Ling, Yawei Kong, Sara Roberson, Marnie E Halpern, Eric C LiaoAbstract:The Wnt signaling pathway is crucial for tissue morphogenesis, participating in cellular behavior changes, notably during the process of Convergent-Extension. Interactions between Wnt-secreting and receiving cells during Convergent-Extension remain elusive. We investigated the role and genetic interactions of Wnt ligands and their trafficking factors Wls, Gpc4 and Frzb in the context of palate morphogenesis in zebrafish. We describe that the chaperon Wls and its ligands Wnt9a and Wnt5b are expressed in the ectoderm, whereas juxtaposed chondrocytes express Frzb and Gpc4. Using wls, gpc4, frzb, wnt9a and wnt5b mutants, we genetically dissected the Wnt signals operating between secreting ectoderm and receiving chondrocytes. Our analysis delineates that non-canonical Wnt signaling is required for cell intercalation, and that wnt5b and wnt9a are required for palate Extension in the anteroposterior and transverse axes, respectively.
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neural tube closure requires dishevelled dependent Convergent Extension of the midline
Development, 2002Co-Authors: John B Wallingford, Richard M HarlandAbstract:In Xenopus, Dishevelled (Xdsh) signaling is required for both neural tube closure and neural Convergent Extension, but the connection between these two morphogenetic processes remains unclear. Indeed normal neurulation requires several different cell polarity decisions, any of which may require Xdsh signaling. In this paper we address two issues: (1) which aspects of normal neurulation require Xdsh function; and (2) what role Convergent Extension plays in the closure of the neural tube. We show that Xdsh signaling is not required for neural fold elevation, medial movement or fusion. Disruption of Xdsh signaling therefore provides a specific tool for uncoupling Convergent Extension from other processes of neurulation. Using disruption of Xdsh signaling, we demonstrate that Convergent Extension is crucial to tube closure. Targeted injection revealed that Xdsh function was required specifically in the midline for normal neural tube closure. We suggest that the inherent movement of the neural folds can accomplish only a finite amount of medial progress and that Convergent Extension of the midline is necessary to reduce the distance between the nascent neural folds, allowing them to meet and fuse. Similar results with Xenopus strabismus implicate the planar cell polarity (PCP) signaling cascade in neural Convergent Extension and tube closure. Together, these data demonstrate that PCP-mediated Convergent Extension movements are crucial to proper vertebrate neurulation.
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Convergent Extension the molecular control of polarized cell movement during embryonic development
Developmental Cell, 2002Co-Authors: John B Wallingford, Scott E Fraser, Richard M HarlandAbstract:During development, vertebrate embryos undergo dramatic changes in shape. The lengthening and narrowing of a field of cells, termed Convergent Extension, contributes to a variety of morphogenetic processes. Focusing on frogs and fish, we review the different cellular mechanisms and the well-conserved signaling pathways that underlie this process.
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xenopus dishevelled signaling regulates both neural and mesodermal Convergent Extension parallel forces elongating the body axis
Development, 2001Co-Authors: John B Wallingford, Richard M HarlandAbstract:During amphibian development, non-canonical Wnt signals regulate the polarity of intercalating dorsal mesoderm cells during Convergent Extension. Cells of the overlying posterior neural ectoderm engage in similar morphogenetic cell movements. Important differences have been discerned in the cell behaviors associated with neural and mesodermal cell intercalation, raising the possibility that different mechanisms may control intercalations in these two tissues. In this report, targeted expression of mutants of Xenopus Dishevelled ( Xdsh ) to neural or mesodermal tissues elicited different defects that were consistent with inhibition of either neural or mesodermal Convergent Extension. Expression of mutant Xdsh also inhibited elongation of neural tissues in vitro in Keller sandwich explants and in vivo in neural plate grafts. Targeted expression of other Wnt signaling antagonists also inhibited neural Convergent Extension in whole embryos. In situ hybridization indicated that these defects were not due to changes in cell fate. Examination of embryonic phenotypes after inhibition of Convergent Extension in different tissues reveals a primary role for mesodermal Convergent Extension in axial elongation, and a role for neural Convergent Extension as an equalizing force to produce a straight axis. This study demonstrates that non-canonical Wnt signaling is a common mechanism controlling Convergent Extension in two very different tissues in the Xenopus embryo and may reflect a general conservation of control mechanisms in vertebrate Convergent Extension.
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calcium signaling during Convergent Extension in xenopus
Current Biology, 2001Co-Authors: John B Wallingford, Andrew J Ewald, Richard M Harland, Scott E FraserAbstract:Background: During Xenopus gastrulation, cell intercalation drives Convergent Extension of dorsal tissues. This process requires the coordination of motility throughout a large population of cells. The signaling mechanisms that regulate these movements in space and time remain poorly understood. Results: To investigate the potential contribution of calcium signaling to the control of morphogenetic movements, we visualized calcium dynamics during Convergent Extension using a calcium-sensitive fluorescent dye and a novel confocal microscopy system. We found that dramatic intercellular waves of calcium mobilization occurred in cells undergoing Convergent Extension in explants of gastrulating Xenopus embryos. These waves arose stochastically with respect to timing and position within the dorsal tissues. Waves propagated quickly and were often accompanied by a wave of contraction within the tissue. Calcium waves were not observed in explants of the ventral marginal zone or prospective epidermis. Pharmacological depletion of intracellular calcium stores abolished the calcium dynamics and also inhibited Convergent Extension without affecting cell fate. These data indicate that calcium signaling plays a direct role in the coordination of Convergent Extension cell movements. Conclusions: The data presented here indicate that intercellular calcium signaling plays an important role in vertebrate Convergent Extension. We suggest that calcium waves may represent a widely used mechanism by which large groups of cells can coordinate complex cell movements.
Carlphilipp Heisenberg - One of the best experts on this subject based on the ideXlab platform.
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Convergent Extension using collective cell migration and cell intercalation to shape embryos
Development, 2012Co-Authors: Masazumi Tada, Carlphilipp HeisenbergAbstract:Body axis elongation represents a common and fundamental morphogenetic process in development. A key mechanism triggering body axis elongation without additional growth is Convergent Extension (CE), whereby a tissue undergoes simultaneous narrowing and Extension. Both collective cell migration and cell intercalation are thought to drive CE and are used to different degrees in various species as they elongate their body axis. Here, we provide an overview of CE as a general strategy for body axis elongation and discuss conserved and divergent mechanisms underlying CE among different species.
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silberblick wnt11 mediates Convergent Extension movements during zebrafish gastrulation
Nature, 2000Co-Authors: Carlphilipp Heisenberg, Masazumi Tada, Gerdjorg Rauch, Leonor Saude, Miguel L Concha, Robert Geisler, Derek L Stemple, J C Smith, Stephen W WilsonAbstract:Vertebrate gastrulation involves the specification and coordinated movement of large populations of cells that give rise to the ectodermal, mesodermal and endodermal germ layers. Although many of the genes involved in the specification of cell identity during this process have been identified, little is known of the genes that coordinate cell movement. Here we show that the zebrafish silberblick (slb) locus1 encodes Wnt11 and that Slb/Wnt11 activity is required for cells to undergo correct Convergent Extension movements during gastrulation. In the absence of Slb/Wnt11 function, abnormal Extension of axial tissue results in cyclopia and other midline defects in the head2. The requirement for Slb/Wnt11 is cell non-autonomous, and our results indicate that the correct Extension of axial tissue is at least partly dependent on medio-lateral cell intercalation in paraxial tissue. We also show that the slb phenotype is rescued by a truncated form of Dishevelled that does not signal through the canonical Wnt pathway3, suggesting that, as in flies4, Wnt signalling might mediate morphogenetic events through a divergent signal transduction cascade. Our results provide genetic and experimental evidence that Wnt activity in lateral tissues has a crucial role in driving the Convergent Extension movements underlying vertebrate gastrulation.
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Silberblick/Wnt11 mediates Convergent Extension movements during zebrafish gastrulation.
Nature, 2000Co-Authors: Carlphilipp Heisenberg, Masazumi Tada, Gerdjorg Rauch, Leonor Saude, Miguel L Concha, Robert Geisler, Derek L Stemple, J C Smith, Stephen W WilsonAbstract:Vertebrate gastrulation involves the specification and coordinated movement of large populations of cells that give rise to the ectodermal, mesodermal and endodermal germ layers. Although many of the genes involved in the specification of cell identity during this process have been identified, little is known of the genes that coordinate cell movement. Here we show that the zebrafish silberblick (slb) locus1 encodes Wnt11 and that Slb/Wnt11 activity is required for cells to undergo correct Convergent Extension movements during gastrulation. In the absence of Slb/Wnt11 function, abnormal Extension of axial tissue results in cyclopia and other midline defects in the head2. The requirement for Slb/Wnt11 is cell non-autonomous, and our results indicate that the correct Extension of axial tissue is at least partly dependent on medio-lateral cell intercalation in paraxial tissue. We also show that the slb phenotype is rescued by a truncated form of Dishevelled that does not signal through the canonical Wnt pathway3, suggesting that, as in flies4, Wnt signalling might mediate morphogenetic events through a divergent signal transduction cascade. Our results provide genetic and experimental evidence that Wnt activity in lateral tissues has a crucial role in driving the Convergent Extension movements underlying vertebrate gastrulation.