XB-ART-51112
PLoS One
2015 Aug 13;108:e0135504. doi: 10.1371/journal.pone.0135504.
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Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway.
Abstract
Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.
PubMed ID: 26270962
PMC ID: PMC4536202
Article link: PLoS One
Species referenced: Xenopus laevis
Genes referenced: atf2 chrd ctnnb1 dvl2 fzd7 krt12.4 mapk8 mcf2 myc myod1 nodal3.2 otx2 pkdcc.1 pkdcc.2 sia1 snai2 sox2 tbxt tnni3 wnt11 wnt5a wnt8a
Morpholinos: pkdcc.1 MO1 pkdcc.2 MO1
Phenotypes: Xla Wt + LiCl (fig.3.c, d) [+]
Xla Wt + LiCl
(fig.3.g, h)
Xla Wt + UV (fig.3.b)
Xla Wt + UV (fig.3.f)
Xla Wt + pkdcc.1 MO (fig.10.b)
Xla Wt + pkdcc.1 MO (fig.10.i)
Xla Wt + pkdcc.1 MO (fig.4.d)
Xla Wt + pkdcc.1 MO (fig.4.e, f, f^1, f^2)
Xla Wt + pkdcc.1 MO (fig.5.h, k, n, q, t)
Xla Wt + pkdcc.1 MO (fig.S1.b)
Xla Wt + pkdcc.1 MO (fig.S1.d)
Xla Wt + pkdcc.1 MO (fig.S2.b)
Xla Wt + pkdcc.1 MO (fig.S2.g)
Xla Wt + pkdcc.2 MO (fig.10.e)
Xla Wt + pkdcc.2 MO (fig.10.l)
Xla Wt + pkdcc.2 MO (fig.4.g)
Xla Wt + pkdcc.2 MO (fig.4.h, i, i^1)
Xla Wt + pkdcc.2 MO (fig.5.i, l, o, r, u)
Xla Wt + pkdcc.2 MO (fig.S1.c)
Xla Wt + pkdcc.2 MO (fig.S1.e)
Xla Wt + pkdcc.2 MO (fig.S2.d)
Xla Wt + pkdcc.2 MO (fig.S2.i)
Xla Wt + UV (fig.3.b)
Xla Wt + UV (fig.3.f)
Xla Wt + pkdcc.1 MO (fig.10.b)
Xla Wt + pkdcc.1 MO (fig.10.i)
Xla Wt + pkdcc.1 MO (fig.4.d)
Xla Wt + pkdcc.1 MO (fig.4.e, f, f^1, f^2)
Xla Wt + pkdcc.1 MO (fig.5.h, k, n, q, t)
Xla Wt + pkdcc.1 MO (fig.S1.b)
Xla Wt + pkdcc.1 MO (fig.S1.d)
Xla Wt + pkdcc.1 MO (fig.S2.b)
Xla Wt + pkdcc.1 MO (fig.S2.g)
Xla Wt + pkdcc.2 MO (fig.10.e)
Xla Wt + pkdcc.2 MO (fig.10.l)
Xla Wt + pkdcc.2 MO (fig.4.g)
Xla Wt + pkdcc.2 MO (fig.4.h, i, i^1)
Xla Wt + pkdcc.2 MO (fig.5.i, l, o, r, u)
Xla Wt + pkdcc.2 MO (fig.S1.c)
Xla Wt + pkdcc.2 MO (fig.S1.e)
Xla Wt + pkdcc.2 MO (fig.S2.d)
Xla Wt + pkdcc.2 MO (fig.S2.i)
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ig 1. PKDCC protein family encode for a Serine/threonine/tyrosine protein kinase catalytic domain. Comparison of the predicted amino acid sequence of mouse (M. musculus) PKDCC with its X. laevis orthologs, Pkdcc1 and Pkdcc2. pkdcc1 encodes a 449 a.a. protein with a predicted molecular mass of 51.0 kDa and pkdcc2 encodes for a protein with 489 a.a. and 55.9 kDa of predicted molecular mass. Bioinformatic analysis showed that both proteins contain the Serine/Threonine/Tyrosine protein kinase catalytic domain (between a.a. 89 and 336 for Pkdcc1 and between a.a 134 and 381 for Pkdcc2; Grey box, STYKc domain). Identical amino acids among all are shown in red while identical amino acids in only two sequences are shown in blue. The absence of residues at the corresponding region is indicated by dashes. |
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Fig 2. pkdcc1 and pkdcc2 expression patterns during X. laevis embryonic development. (A-H) Expression pattern of pkdcc1 during early development. (I) Temporal expression pattern of Xenopus pkdcc1 and pkdcc2 analysed by quantitative PCR. GAPDH was used as reference gene. (J-O’) Expression pattern of pkdcc2 during Xenopus development. By early gastrula stages, pkdcc1 transcripts can be detected in the (A) dorsal blastopore lip and (B) ADE. (C) At stage 12, pkdcc1 is present in the involuting mesoderm. (D) During neurula stages pkdcc1 is expressed in neural folds and eye fields. (E-F’) pkdcc1 expression at tailbud stages is restricted to the lateral plate mesoderm, foregut, eye and isthmus. (G) Double whole mount in situ hybridization for pkdcc1 (blue) and otx2 (red) shows that pkdcc1 expression in the brain is restricted to the mid-hindbrain boundary. (H) Double whole mount in situ hybridization for pkdcc1 (blue) and cardiac troponin (red) showed that pkdcc1 expression is absent on the heart. (J) Zygotic pkdcc2 is detectable at early gastrula stages in the anterior dorsal endoderm. (K) At late-gastrula stages pkdcc2 mRNA is expressed in the involuting mesoderm. (L) During early neurula stages, pkdcc2 transcripts can be detected in the neural folds (dorsal view, anterior down). (M) At stage 17, pkdcc2 is co-expressed with pkdcc1 in the prospective eye field and neural folds. (N-O’) In tailbud stages (27 and 31; lateral view, anterior to the right and dorsal up), pkdcc2 is expressed in the neural tube roof, otic vesicle, notochord, eye, lateral plate mesoderm and head mesenchyme. D, dorsal; V, ventral; A, anterior; P, posterior. |
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Fig 3. Expression of both pkdcc1 and pkdcc2 is induced downstream of Wnt canonical signaling. (A-H) Axis perturbation assay. Whole-mount in situ hybridization of gastrula stages untreated embryos (A, E) or treated with UV (B, F) or LiCl (C, D, G, H) and hybridized with (A-D) pkdcc1 or (E-H) pkdcc2 probe. Embryos are shown in a vegetal view with the dorsal side at the top and ventral side at the bottom. Hemisections are displayed with the dorsal side to the right. (I) qPCR for pkdcc1 and pkdcc2 expression on wild type embryos and uninjected and β-catenin or wnt8 injected animal caps. (J) qPCR analysis of xnr3 and siamois (sia) expression on wild type embryos and uninjected and pkdcc1 or pkdcc2 injected animal caps. D, dorsal; V, ventral. (p<0.05, in the Student’s t-test). |
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Fig 4. In vivo requirement of Pkdcc1 and Pkdcc2 during early development. (A-I”) Four cell stages were injected either (A, D, G) dorsally or (B-C, E-F”, H-I”) unilaterally with (D-F”) pkdcc1Mo, (G-I”) pkdcc2Mo or (A-C) coMo and analysed at (A, D, G) stage 13, (B, E, H) 15 or (C, F-F”, I-I”) 18/19. Injection of pkdcc1Mo and pkdcc2Mo caused (D, G) gastrulation and (E-F, H-I) neural tube closure defects that were not observed in (A-C) coMo injected embryos. (F’-F”, I’-I”) Magnification of the stage 18/19 pkdcc1Mo and pkdcc2Mo unilaterally injected embryos. Yellow and red arrows show the delay of neural fold formation. A, anterior; P, posterior; D, dorsal; V, ventral; inj, injected side; co, uninjected side. |
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Fig 5. Absence of Pkdcc1 and Pkdcc2 does not change cell fate of mesoderm and neural tissues. Whole mount in situ hybridization for Xbra (A-C) and chd (D-F) of embryos injected with CoMo (A, D), pkdcc1Mo (B, E) or pkdcc2Mo (C, F) in the dorsal blastomeres. Whole mount in situ hybridization for myoD (G-I), slug (J-L), epk/chd (M-O), otx2 (P-R) and sox2 (S-U) of embryos injected with CoMo (G, J, M, P, S), pkdcc1Mo (H, K, N, Q, T) or pkdcc2Mo (I, L, O, R, U) in the right side. (A-F) Vegetal view of gastrula stage embryos with dorsal to the top. (G-U) Anterior view of embryos from late gastrula (G-I) to neurula stages (J-U) with dorsal to the top. inj, injected side; co, uninjected side. |
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Fig 6. Effect of Pkdccs downregulation on convergent extension movements. (A) the percentage of elongated animal caps. -, no elongation; +/- partial elongation; +, strong elongation. (B) Uninjected animal caps without activin treatment. Uninjected (C) or injected animal caps with (D) coMo, (E) pkdcc1Mo or (F) pkdcc2Mo treated with activin. (G) qPCR analysis of mesodermal markers chd, myoD and xbra expression on wild type embryos at st 14 and uninjected or coMo, pkdcc1Mo or pkdcc2Mo injected animal caps in the presence of activin. |
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Fig 7. Both Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. (A-O) Embryos were injected with the indicated mRNAs, the ectodermal explants were extracted and Dvl.GFP localization was observed by confocal microscopy. Dvl tagged with GFP (green) is shown on the left panel, the membrane bound RFP (mbRFP, red) is shown on the middle panel and the merge pictures are shown on the right panel. (A-C) Dvl.GFP is localized in the cytoplasm of animal cap cells injected with 300 pg of dvl.GFP mRNA. (D-F) When 300 pg of dvl.GFP mRNA are co-injected with 150 pg of fz7 RNA, Dvl.GFP is recruited to the membrane. (G-I) Co-injection of 500 pg pkdcc1 RNA and 300 pg of dvl.GFP mRNA leads to membrane recruitment of Dvl.GFP as well as (J-L) the co-injection of 500 pg of pkdcc2 mRNA and 300 pg of dvl.GFP mRNA. (M-O) the same membrane localization of Dvl.GFP is observed when 300pg of dvl.GFP mRNA are co-injected with 500 pg of each pkdcc1 and pkdcc2 mRNAs. |
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Fig 8. Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane through DEP domain. (A) Schematic representation of Dvl domains involved in both Wnt canonical and non-canonical signaling pathways, and DEP.Dvl construct containing the DEP domain of Dvl fused to GFP reporter. (B-P) Embryos were injected with the indicated RNAs, the ectodermal explants were extracted and DEP.Dvl localization was observed by confocal microscopy. DEP domain tagged with GFP (green) is shown on the left panel, the membrane bound RFP (mbRFP, red) is shown on the middle panel and the merged pictures are shown in the right panel. (B-D) DEP.Dvl is localized in the cytoplasm of cells when is overexpressed alone but is recruited to the plasma membrane when co-overexpressed with fz7 (E-G). Co-injection of DEP.dvl and pkdcc1 (H-J), pkdcc2 (K-M) or both simultaneously (N-P) leads to the membrane recruitment of DEP.Dvl. |
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Fig 9. Pkdcc1 is an inducer of PCP signaling while Pkdcc2 is a repressor. (A, B) HEK293T cells were transfected with the indicated constructs in addition to an ATF2 luciferase reporter construct and a β-galactosidase expression vector. Luciferase activity was measured 48h after transfection and normalized with β-galactosidase activity. Each experiment was carried out in triplicates and error bars represent the standard deviation. (C) X. laevis embryos were injected radially at two cell stage with the indicated constructs in addition to an ATF2 luciferase reporter construct and a β-galactosidase expression vector. Luciferase activity was measured at gastrula stages (st11) and normalized with β-galactosidase activity. Error bars represent the standard deviation of the mean. |
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Fig 10. Rescue of pkdcc1Mo and pkdcc2Mo phenotype by JNK and dnJNK, respectively. (A- G) Four cell stage embryos were injected dorsally with coMo (A), pkdcc1Mo (B-D) or pkdcc2Mo (E-G) and incubated until blastopore closure. The pkdcc1Mo phenotype (delay in blastopore closure) was rescued by injection with JNK mRNA (C) but not with dominant negative JNK (dnJNK) mRNA(D). Contrary, pkdcc2Mo phenotype was rescued by the injection with the dnJNK mRNAbut not with JNK mRNA. (H-N) Four cell stage embryos were unilaterally injected with coMo (H), pkdcc1Mo (I-K) or pkdcc2Mo (L-N) and incubated until neural tube closure. Once again, the phenotype observed in the absence of Pkdcc1 (delay in neural tube closure) was rescued by the overexpression of JNK mRNA (J) but not of dnJNK mRNA (K). Contrary, pkdcc2Mo phenotype was rescued by co-injection of dnJNK mRNA (M) but not of JNK mRNA (N). |
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S1 Fig. Hemi-sections of Pkdcc1 and Pkdcc2 knockdown embryos during gastrula and neurula stages. (A-C) Hemi-section of X.laevis embryos injected dorsally with CoMo (A), pkdcc1Mo (B) or pkdcc2Mo (C) at gastrula stage. Auto-fluorescence of the embryo was observed by confocal microscopy. Dorsal to the left and animal to the top (A’-C’). Schematic representation of embryos A-C, respectively. (D, E) Hemisection of X.laevis embryos injected unilaterally with pkdcc1Mo (D) or pkdcc2Mo (E). Auto-fluorescence of the embryo was observed by confocal microscopy. Dorsal to the top. (D’, E’) Schematic representation of embryos D, E, respectively. bc, bottle cells; idm, involuting dorsal mesoderm; dbl, dorsal blastopore lip; sm, presomitic mesoderm; nc, neural crest; e, endoderm. |
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S2 Fig. Rescue of pkdcc1Mo and pkdcc2Mo phenotype by pkdcc1(mut) and pkdcc2(mut) mRNAs, respectively. (A-E) Four cell stage embryos were injected dorsally with coMo (A), pkdcc1Mo (B) or pkdcc2Mo (D) and incubated until blastopore closure. The pkdcc1Mo phenotype was rescued by co-injection with 1ng of pkdcc1(mut) mRNA (C) and pkdcc2Mo phenotype was rescued by the co-injection with the 1ng of pkdcc2(mut) mRNA. (F-J) Four cell stage embryos were unilaterally injected with pkdcc1Mo (G), pkdcc2Mo (I) or coMo (F) and incubated until neural tube closure. Once again, the phenotype obtained by the absence of Pkdcc1 was rescued by the overexpression of pkdcc1(mut) mRNA (H) and pkdcc2Mo phenotype was rescued by co-injection of pkdcc2(mut) mRNA (J). n is the number of injected embryos and the percentage stands for the embryos with the observed defect. |
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S3 Fig. Co-localization of Rab8, Pkdcc1 and Pkdcc2 in the Golgi apparatus. Transfection of HEK293T cells with (A-C) Rab8.GFP (50 ng) and Pkdcc1.HA (1 μg) or (D-F) with Rab8.GFP (50 ng) and Pkdcc2.myc (1 μg). Immunofluorescence against HA (B) and myc (E) was performed. Overlay of Rab8 and Pkdcc1 (C) or Pkdcc2 (F) are represented in the right side of the panel. |
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pkdcc.1 (protein kinase domain containing, cytoplasmic homolog, gene 1) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 26, lateral view, anterior right, dorsal up. |
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pkdcc.2 (protein kinase domain containing, cytoplasmic) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 26, lateral view, anterior right, dorsal up. |
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Fig 1. PKDCC protein family encode for a Serine/threonine/tyrosine protein kinase catalytic domain.Comparison of the predicted amino acid sequence of mouse (M. musculus) PKDCC with its X. laevis orthologs, Pkdcc1 and Pkdcc2. pkdcc1 encodes a 449 a.a. protein with a predicted molecular mass of 51.0 kDa and pkdcc2 encodes for a protein with 489 a.a. and 55.9 kDa of predicted molecular mass. Bioinformatic analysis showed that both proteins contain the Serine/Threonine/Tyrosine protein kinase catalytic domain (between a.a. 89 and 336 for Pkdcc1 and between a.a 134 and 381 for Pkdcc2; Grey box, STYKc domain). Identical amino acids among all are shown in red while identical amino acids in only two sequences are shown in blue. The absence of residues at the corresponding region is indicated by dashes. |
References [+] :
Acampora,
Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation.
1995, Pubmed
Acampora, Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. 1995, Pubmed
Angers, Proximal events in Wnt signal transduction. 2009, Pubmed
Axelrod, Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. 2001, Pubmed
Axelrod, Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. 1998, Pubmed , Xenbase
Baker, A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. 1996, Pubmed , Xenbase
Belo, Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. 1997, Pubmed , Xenbase
Boutros, Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. 1998, Pubmed
Boutros, Dishevelled: at the crossroads of divergent intracellular signaling pathways. 1999, Pubmed , Xenbase
Bouwmeester, Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer. 1996, Pubmed , Xenbase
Cai, Genetic evidence in planar cell polarity signaling pathway in human neural tube defects. 2014, Pubmed
Choi, The involvement of lethal giant larvae and Wnt signaling in bottle cell formation in Xenopus embryos. 2009, Pubmed , Xenbase
Copp, Dishevelled: linking convergent extension with neural tube closure. 2003, Pubmed , Xenbase
Doudney, Analysis of the planar cell polarity gene Vangl2 and its co-expressed paralogue Vangl1 in neural tube defect patients. 2005, Pubmed
Drysdale, Cardiac troponin I is a heart-specific marker in the Xenopus embryo: expression during abnormal heart morphogenesis. 1994, Pubmed , Xenbase
Epstein, Patterning of the embryo along the anterior-posterior axis: the role of the caudal genes. 1997, Pubmed , Xenbase
Gao, Wnt regulation of planar cell polarity (PCP). 2012, Pubmed
Gao, Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. 2011, Pubmed
Gonçalves, Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm. 2011, Pubmed
Goto, The planar cell polarity gene strabismus regulates convergence and extension and neural fold closure in Xenopus. 2002, Pubmed , Xenbase
Habas, Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. 2001, Pubmed , Xenbase
Habas, Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. 2003, Pubmed , Xenbase
Haigo, Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. 2003, Pubmed , Xenbase
Heasman, Morpholino oligos: making sense of antisense? 2002, Pubmed , Xenbase
Imuta, Short limbs, cleft palate, and delayed formation of flat proliferative chondrocytes in mice with targeted disruption of a putative protein kinase gene, Pkdcc (AW548124). 2009, Pubmed
Itoh, Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction. 2000, Pubmed , Xenbase
Jessen, Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. 2002, Pubmed
Keller, How we are shaped: the biomechanics of gastrulation. 2003, Pubmed , Xenbase
Keller, Mechanisms of convergence and extension by cell intercalation. 2000, Pubmed
Kibar, Identification of a new chemically induced allele (Lp(m1Jus)) at the loop-tail locus: morphology, histology, and genetic mapping. 2001, Pubmed
Kibar, Mutations in VANGL1 associated with neural-tube defects. 2007, Pubmed
Kim, Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. 2010, Pubmed , Xenbase
Kinoshita, The novel protein kinase Vlk is essential for stromal function of mesenchymal cells. 2009, Pubmed
Klein, A molecular mechanism for the effect of lithium on development. 1996, Pubmed , Xenbase
Kumburegama, Strabismus-mediated primary archenteron invagination is uncoupled from Wnt/β-catenin-dependent endoderm cell fate specification in Nematostella vectensis (Anthozoa, Cnidaria): Implications for the evolution of gastrulation. 2011, Pubmed
Kurth, Bottle cell formation in relation to mesodermal patterning in the Xenopus embryo. 2000, Pubmed , Xenbase
Lapébie, Dissecting the PCP pathway: one or more pathways?: Does a separate Wnt-Fz-Rho pathway drive morphogenesis? 2011, Pubmed , Xenbase
Lee, Uncorking gastrulation: the morphogenetic movement of bottle cells. 2012, Pubmed , Xenbase
Lopes, The ternary Rab27a-Myrip-Myosin VIIa complex regulates melanosome motility in the retinal pigment epithelium. 2007, Pubmed
Lustig, Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal patterning and blastopore lip formation. 1996, Pubmed , Xenbase
Matthews, Directional migration of neural crest cells in vivo is regulated by Syndecan-4/Rac1 and non-canonical Wnt signaling/RhoA. 2008, Pubmed , Xenbase
Medina, Interaction of Frizzled 7 and Dishevelled in Xenopus. 2000, Pubmed , Xenbase
Medina, Xenopus frizzled 7 can act in canonical and non-canonical Wnt signaling pathways: implications on early patterning and morphogenesis. 2000, Pubmed , Xenbase
Mlodzik, Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? 2002, Pubmed
Morita, Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis. 2010, Pubmed , Xenbase
Muñoz, Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension movements in Xenopus embryos. 2006, Pubmed , Xenbase
Ohkawara, An ATF2-based luciferase reporter to monitor non-canonical Wnt signaling in Xenopus embryos. 2011, Pubmed , Xenbase
Pannese, The Xenopus homologue of Otx2 is a maternal homeobox gene that demarcates and specifies anterior body regions. 1995, Pubmed , Xenbase
Perestrelo, Novel triblock co-polymer nanofibre system as an alternative support for embryonic stem cells growth and pluripotency. 2016, Pubmed
Poliakov, Ephrins make eyes with planar cell polarity. 2006, Pubmed , Xenbase
Probst, The hedgehog target Vlk genetically interacts with Gli3 to regulate chondrocyte differentiation during mouse long bone development. 2013, Pubmed
Rothbächer, Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. 2000, Pubmed , Xenbase
Sheldahl, Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. 1999, Pubmed , Xenbase
Shnitsar, PTK7 recruits dsh to regulate neural crest migration. 2008, Pubmed , Xenbase
Silva, Characterization of Cer-1 cis-regulatory region during early Xenopus development. 2011, Pubmed , Xenbase
Simons, Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization. 2009, Pubmed
Summerton, Morpholino antisense oligomers: design, preparation, and properties. 1997, Pubmed , Xenbase
Thomas, Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. 1996, Pubmed
Torres, Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development. 1996, Pubmed , Xenbase
Vladar, Planar cell polarity signaling: the developing cell's compass. 2009, Pubmed
Wallingford, Xenopus Dishevelled signaling regulates both neural and mesodermal convergent extension: parallel forces elongating the body axis. 2001, Pubmed , Xenbase
Wallingford, Convergent extension: the molecular control of polarized cell movement during embryonic development. 2002, Pubmed , Xenbase
Wallingford, The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity. 2005, Pubmed
Wallingford, Neural tube closure requires Dishevelled-dependent convergent extension of the midline. 2002, Pubmed , Xenbase
Wang, Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. 2006, Pubmed , Xenbase
Wansleeben, The planar cell polarity pathway in vertebrate development. 2011, Pubmed
Wu, A quest for the mechanism regulating global planar cell polarity of tissues. 2009, Pubmed
Yamanaka, JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. 2002, Pubmed , Xenbase
Yanagawa, The dishevelled protein is modified by wingless signaling in Drosophila. 1995, Pubmed