dusp6

Summary

Gene Symbol: dusp6
Description: dual specificity phosphatase 6
Alias: Mkp3, wu:fd99d09, dual specificity protein phosphatase 6, etID14116.25
Species: zebrafish
Products:     dusp6

Top Publications

  1. Hashiguchi M, Shinya M, Tokumoto M, Sakai N. Nodal/Bozozok-independent induction of the dorsal organizer by zebrafish cell lines. Dev Biol. 2008;321:387-96 pubmed publisher
    ..Finally, the Nodal signaling pathway was not activated following implantation of cultured cells. Collectively, these data suggest that zebrafish cell lines induce the dorsal organizer independent of the boz and Nodal signaling pathways. ..
  2. Molina G, Vogt A, Bakan A, Dai W, Queiroz de Oliveira P, Znosko W, et al. Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat Chem Biol. 2009;5:680-7 pubmed publisher
    The dual-specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth factor (FGF) signaling to limit the activity of extracellular signal-regulated kinases (ERKs) 1 and 2...
  3. Blum N, Begemann G. Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration. Development. 2012;139:107-16 pubmed publisher
  4. Tsang M, Maegawa S, Kiang A, Habas R, Weinberg E, Dawid I. A role for MKP3 in axial patterning of the zebrafish embryo. Development. 2004;131:2769-79 pubmed
    ..We report the characterization of zebrafish MAP kinase phosphatase 3 (MKP3; DUSP6 - Zebrafish Information Network), a member of the FGF synexpression group, showing that it has a crucial role in ..
  5. Ignatius M, Chen E, Elpek N, Fuller A, Tenente I, Clagg R, et al. In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma. Cancer Cell. 2012;21:680-93 pubmed publisher
    ..Our data suggest that non-tumor-propagating cells likely have important supportive roles in cancer progression and facilitate metastasis. ..
  6. Van Raay T, Coffey R, Solnica Krezel L. Zebrafish Naked1 and Naked2 antagonize both canonical and non-canonical Wnt signaling. Dev Biol. 2007;309:151-68 pubmed
    ..Finally, reducing Nkd1 function in slb mutants suppressed the axial mesendoderm C&E defect. These data indicate that zebrafish Nkd1 and Nkd2 function to limit both canonical and non-canonical Wnt signaling. ..
  7. Varga M, Maegawa S, Bellipanni G, Weinberg E. Chordin expression, mediated by Nodal and FGF signaling, is restricted by redundant function of two beta-catenins in the zebrafish embryo. Mech Dev. 2007;124:775-91 pubmed
  8. Maegawa S, Varga M, Weinberg E. FGF signaling is required for {beta}-catenin-mediated induction of the zebrafish organizer. Development. 2006;133:3265-76 pubmed
  9. Kawakami Y, Rodriguez Esteban C, Raya M, Kawakami H, Marti M, Dubova I, et al. Wnt/beta-catenin signaling regulates vertebrate limb regeneration. Genes Dev. 2006;20:3232-7 pubmed
    ..Our studies may provide valuable insights toward a better understanding of adult tissue regeneration. ..

More Information

Publications62

  1. Molina G, Watkins S, Tsang M. Generation of FGF reporter transgenic zebrafish and their utility in chemical screens. BMC Dev Biol. 2007;7:62 pubmed
    ..Expression of Dual Specificity Phosphatase 6 (dusp6, also known as Mkp3) is controlled by FGF signalling throughout development...
  2. Nojima H, Rothhämel S, Shimizu T, Kim C, Yonemura S, Marlow F, et al. Syntabulin, a motor protein linker, controls dorsal determination. Development. 2010;137:923-33 pubmed publisher
    ..Our findings suggest that Syntabulin regulates the microtubule-dependent transport of the DDs, and provide evidence for the link between AV and dorsoventral axis formation. ..
  3. Ganz J, Kaslin J, Hochmann S, Freudenreich D, Brand M. Heterogeneity and Fgf dependence of adult neural progenitors in the zebrafish telencephalon. Glia. 2010;58:1345-63 pubmed publisher
  4. Stewart S, Stankunas K. Limited dedifferentiation provides replacement tissue during zebrafish fin regeneration. Dev Biol. 2012;365:339-49 pubmed publisher
    ..These blastemas each have an organized structure of lineage restricted, dedifferentiated cells that cooperate to regenerate the caudal fin. ..
  5. Lee Y, Grill S, Sanchez A, Murphy Ryan M, Poss K. Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration. Development. 2005;132:5173-83 pubmed
    ..with position-dependent differences in blastemal length, mitotic index and expression of the Fgf target genes mkp3, sef and spry4...
  6. Norton W, Ledin J, Grandel H, Neumann C. HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development. Development. 2005;132:4963-73 pubmed
    ..This reveals an unexpected specificity of HSPGs in regulating distinct vertebrate Fgfs. ..
  7. Kawakami Y, Rodriguez Leon J, Koth C, Buscher D, Itoh T, Raya A, et al. MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb. Nat Cell Biol. 2003;5:513-9 pubmed
    ..Here we show that during chick, mouse and zebrafish limb/fin development, a known MAPK/ERK regulator, Mkp3, is induced in the mesenchyme by fibroblast growth factor 8 (FGF8) signalling, through the PI3K/Akt pathway...
  8. Balciunas D, Davidson A, Sivasubbu S, Hermanson S, Welle Z, Ekker S. Enhancer trapping in zebrafish using the Sleeping Beauty transposon. BMC Genomics. 2004;5:62 pubmed
    ..For example, the ET7 line harbors a transposon insertion near the mkp3 locus and expresses GFP in the midbrain-hindbrain boundary, forebrain and the ventricle, matching a subset of the ..
  9. Akerberg A, Stewart S, Stankunas K. Spatial and temporal control of transgene expression in zebrafish. PLoS ONE. 2014;9:e92217 pubmed publisher
    ..Given the array of existing UAS lines, the modular nature of this system will enable many previously intractable zebrafish experiments. ..
  10. Umasankar P, Sanker S, Thieman J, Chakraborty S, Wendland B, Tsang M, et al. Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning. Nat Cell Biol. 2012;14:488-501 pubmed publisher
    ..Still, the fcho1 morphant phenotype is distinct from severe embryonic defects apparent when AP-2 is depleted. Our data thus challenge the primacy of FCHO1/2 in coat initiation. ..
  11. Aday A, Zhu L, Lakshmanan A, Wang J, Lawson N. Identification of cis regulatory features in the embryonic zebrafish genome through large-scale profiling of H3K4me1 and H3K4me3 binding sites. Dev Biol. 2011;357:450-62 pubmed publisher
  12. Wang G, Cadwallader A, Jang D, Tsang M, Yost H, Amack J. The Rho kinase Rock2b establishes anteroposterior asymmetry of the ciliated Kupffer's vesicle in zebrafish. Development. 2011;138:45-54 pubmed publisher
    ..Live imaging of Tg(dusp6:memGFP)(pt19) transgenic embryos that express GFP in KV cells revealed that rock2b regulates KV cell morphology...
  13. Erickson T, French C, Waskiewicz A. Meis1 specifies positional information in the retina and tectum to organize the zebrafish visual system. Neural Dev. 2010;5:22 pubmed publisher
    ..By patterning both the retina and tectum, Meis1 plays an important role in establishing the retinotectal map and organizing the visual system. ..
  14. Kaslin J, Ganz J, Geffarth M, Grandel H, Hans S, Brand M. Stem cells in the adult zebrafish cerebellum: initiation and maintenance of a novel stem cell niche. J Neurosci. 2009;29:6142-53 pubmed publisher
    ..Nevertheless, retained epithelial properties such as distinct polarization and ventricular contact are critical common determinants to maintain neural stem cell activity in vertebrates. ..
  15. Znosko W, Yu S, Thomas K, Molina G, Li C, Tsang W, et al. Overlapping functions of Pea3 ETS transcription factors in FGF signaling during zebrafish development. Dev Biol. 2010;342:11-25 pubmed publisher
    ..To understand how FGF signaling and ETS factors control gene expression, transcriptional regulation of dusp6 was studied in mouse and zebrafish...
  16. Monteiro J, Aires R, Becker J, Jacinto A, Certal A, Rodr guez Le n J. V-ATPase proton pumping activity is required for adult zebrafish appendage regeneration. PLoS ONE. 2014;9:e92594 pubmed publisher
    ..Notably, the activity of this H+ pump is necessary for aldh1a2 and mkp3 expression, blastema cell proliferation and fin innervation...
  17. Choe C, Crump J. Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a. Development. 2014;141:3583-93 pubmed publisher
    ..We therefore propose a two-step model in which Tbx1 coordinates the Wnt-dependent epithelial destabilization of pouch-forming cells with their collective migration towards Fgf8a-expressing mesodermal guideposts. ..
  18. McGraw H, Culbertson M, Nechiporuk A. Kremen1 restricts Dkk activity during posterior lateral line development in zebrafish. Development. 2014;141:3212-21 pubmed publisher
    ..Based on our data, we propose a novel mechanism in which Kremen1 modulates Wnt activity by restricting the range of secreted Dkk proteins during collective cell migration in the pLLP. ..
  19. Liao W, Cheng C, Hung K, Chiu W, Chen G, Hwang P, et al. Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling. Cell Mol Life Sci. 2013;70:2367-81 pubmed publisher
    ..ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro ..
  20. Topp S, Stigloher C, Komisarczuk A, Adolf B, Becker T, Bally Cuif L. Fgf signaling in the zebrafish adult brain: association of Fgf activity with ventricular zones but not cell proliferation. J Comp Neurol. 2008;510:422-39 pubmed publisher
    ..We report expression of Fgf signals (fgf3,4,8a,8b,17b), receptors (fgfr1-4), and targets (erm, pea3, dusp6, spry1,2,4, and P-ERK) and document that genes of the embryonic fgf8 synexpression group acquire strikingly ..
  21. Rong X, Chen C, Zhou P, Zhou Y, Li Y, Lu L, et al. R-spondin 3 regulates dorsoventral and anteroposterior patterning by antagonizing Wnt/?-catenin signaling in zebrafish embryos. PLoS ONE. 2014;9:e99514 pubmed publisher
    ..Human RSPO3 has similar action when tested in zebrafish embryos. These results suggest that Rspo3 regulates dorsoventral and anteroposterior patterning by negatively regulating the zygotic Wnt/?-catenin signaling in zebrafish embryos. ..
  22. Rengarajan C, Matzke A, Reiner L, Orian Rousseau V, Scholpp S. Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling. PLoS ONE. 2014;9:e86373 pubmed publisher
    ..Therefore, we hypothesize that Fgf8 receiving cells control both, the propagation width and the signal strength of the morphogen...
  23. Nguyen T, Tran V, Sorna V, Eriksson I, Kojima A, Koketsu M, et al. Dimerized glycosaminoglycan chains increase FGF signaling during zebrafish development. ACS Chem Biol. 2013;8:939-48 pubmed publisher
    ..In situ hybridization showed that elongated embryos have elevated expression of the FGF target gene mkp3 but unchanged expression of reporters for other pathways, indicating that FGF/FGFR signaling was specifically ..
  24. Matsuda M, Nogare D, Somers K, Martin K, Wang C, Chitnis A. Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium. Development. 2013;140:2387-97 pubmed publisher
    ..Lef1 determines expression of the FGF signaling inhibitor Dusp6 in leading cells and regulates incorporation of cells into neuromasts; reduction of Dusp6 in leading cells in lef1-..
  25. Hochmann S, Kaslin J, Hans S, Weber A, Machate A, Geffarth M, et al. Fgf signaling is required for photoreceptor maintenance in the adult zebrafish retina. PLoS ONE. 2012;7:e30365 pubmed publisher
    ..Ultimately, rod and cone photoreceptors are regenerated completely. Our study reveals the requirement of Fgf signaling to maintain photoreceptors and for proliferation during regeneration in the adult zebrafish retina. ..
  26. Jurynec M, Grunwald D. SHIP2, a factor associated with diet-induced obesity and insulin sensitivity, attenuates FGF signaling in vivo. Dis Model Mech. 2010;3:733-42 pubmed publisher
    ..We suggest that modulation of FGF signaling may be a principal function of SHIP2 in mammals. ..
  27. Saydmohammed M, Vollmer L, Onuoha E, Vogt A, Tsang M. A high-content screening assay in transgenic zebrafish identifies two novel activators of fgf signaling. Birth Defects Res C Embryo Today. 2011;93:281-7 pubmed publisher
    ..To conclude, we demonstrate the power of automated quantitative high-content imaging to identify small molecule modulators of FGF. ..
  28. Diao J, Wang H, Chang N, Zhou X, Zhu X, Wang J, et al. PEG-PLA nanoparticles facilitate siRNA knockdown in adult zebrafish heart. Dev Biol. 2015;406:196-202 pubmed publisher
    ..This effect was demonstrated by down-regulation of the Aldh1a2 and Dusp6 proteins after intrapleural delivery of nanoparticle-encapsulated siRNAs...
  29. Hong S, Hu P, Marino J, Hufnagel S, Hopkin R, Toromanović A, et al. Dominant-negative kinase domain mutations in FGFR1 can explain the clinical severity of Hartsfield syndrome. Hum Mol Genet. 2016;25:1912-1922 pubmed
    ..This family is one of the clearest examples to date of gene:gene synergistic interactions causing HPE in humans. ..
  30. Dudley A, Tabin C. Deconstructing phosphatases in limb development. Nat Cell Biol. 2003;5:499-501 pubmed
  31. Norton W, Stumpenhorst K, Faus Kessler T, Folchert A, Rohner N, Harris M, et al. Modulation of Fgfr1a signaling in zebrafish reveals a genetic basis for the aggression-boldness syndrome. J Neurosci. 2011;31:13796-807 pubmed publisher
    ..Together, we show that a single genetic locus can underlie the aggression-boldness behavioral syndrome. We also identify one of the neurotransmitter pathways that may mediate clustering of these behaviors. ..
  32. Plaster N, Sonntag C, Schilling T, Hammerschmidt M. REREa/Atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development. Dev Dyn. 2007;236:1891-904 pubmed
    ..We present a model for RERE-dependent patterning in which tissue-specific transcriptional repression, by means of an REREa-HDAC complex, modulates growth factor signaling during embryogenesis. ..
  33. Moreno T, Jappelli R, Izpisua Belmonte J, Kintner C. Retinoic acid regulation of the Mesp-Ripply feedback loop during vertebrate segmental patterning. Dev Biol. 2008;315:317-30 pubmed publisher
    ..These observations suggest that variations in a direct response to RA input may allow for changes in A-P patterning of the segments in different vertebrate species. ..
  34. Leucht C, Stigloher C, Wizenmann A, Klafke R, Folchert A, Bally Cuif L. MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nat Neurosci. 2008;11:641-8 pubmed publisher
    ..Together, these findings highlight a previously unknown mechanism by which a single microRNA fine-tunes late MHB coherence via its co-regulation of patterning activities and neurogenesis...
  35. Van Raay T, Fortino N, Miller B, Ma H, Lau G, Li C, et al. Naked1 antagonizes Wnt signaling by preventing nuclear accumulation of ?-catenin. PLoS ONE. 2011;6:e18650 pubmed publisher
    ..Given the conserved nature of Nkd1, our results shed light on the negative feedback regulation of Wnt signaling through the Nkd1-mediated negative control of nuclear accumulation of ?-catenin. ..
  36. Shin M, Beane T, Quillien A, Male I, Zhu L, Lawson N. Vegfa signals through ERK to promote angiogenesis, but not artery differentiation. Development. 2016;143:3796-3805 pubmed
    ..Together, these studies implicate ERK as a specific effector of Vegfa signaling in the induction of angiogenic genes during sprouting. ..
  37. Han P, Zhou X, Chang N, Xiao C, Yan S, Ren H, et al. Hydrogen peroxide primes heart regeneration with a derepression mechanism. Cell Res. 2014;24:1091-107 pubmed publisher
    ..Mechanistically, elevated H2O2 destabilized the redox-sensitive phosphatase Dusp6 and hence increased the phosphorylation of Erk1/2...
  38. Pascoal S, Esteves de Lima J, Leslie J, Hughes S, Saude L. Notch signalling is required for the formation of structurally stable muscle fibres in zebrafish. PLoS ONE. 2013;8:e68021 pubmed publisher
    ..We propose that by controlling the differentiation of myogenic progenitor cells, Notch signalling might secure the formation of structurally stable muscle fibres in the zebrafish pectoral fin. ..
  39. Varga M, Sass M, Papp D, Takacs Vellai K, Kobolak J, Dinnyes A, et al. Autophagy is required for zebrafish caudal fin regeneration. Cell Death Differ. 2014;21:547-56 pubmed publisher
    ..This novel cellular function of the autophagic process in regeneration implies that the role of cellular self-digestion in differentiation and tissue patterning is more fundamental than previously thought. ..
  40. Poulain M, Fürthauer M, Thisse B, Thisse C, Lepage T. Zebrafish endoderm formation is regulated by combinatorial Nodal, FGF and BMP signalling. Development. 2006;133:2189-200 pubmed
    ..These results identify a molecular mechanism whereby FGF attenuates Nodal-induced endodermal transcription factors and highlight a potential mechanism whereby mesoderm and endoderm fates could segregate from each other. ..
  41. Roberson S, Halpern M. Convergence of signaling pathways underlying habenular formation and axonal outgrowth in zebrafish. Development. 2017;144:2652-2662 pubmed publisher
    ..The results define a signaling network underlying the generation of dHb neurons and connectivity with their midbrain target. ..
  42. Missinato M, Saydmohammed M, Zuppo D, Rao K, Opie G, Kühn B, et al. Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration. Development. 2018;145: pubmed publisher
    ..the Ras/MAPK pathway, which is tightly controlled by the feedback attenuator Dual specificity phosphatase 6 (Dusp6), an ERK phosphatase. Here, we show that suppressing Dusp6 function enhances cardiac regeneration...
  43. Maier E, Whitfield T. RA and FGF signalling are required in the zebrafish otic vesicle to pattern and maintain ventral otic identities. PLoS Genet. 2014;10:e1004858 pubmed publisher
    ..In addition, our results indicate that FGF and RA signalling act in a feedback loop in the anterior OV, crucial for pattern refinement. ..
  44. Dai W, Bai Y, Hebda L, Zhong X, Liu J, Kao J, et al. Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation. Cell Death Differ. 2014;21:568-81 pubmed publisher
    ..These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca(2+) deficiency. ..
  45. Wu S, Shin J, Sepich D, Solnica Krezel L. Chemokine GPCR signaling inhibits ?-catenin during zebrafish axis formation. PLoS Biol. 2012;10:e1001403 pubmed publisher
    ..Our study delineates a novel negative, Gsk3?-independent control mechanism of ?-catenin and implicates Ccr7 as a long-hypothesized GPCR regulating vertebrate axis formation. ..
  46. Sorrell M, Waxman J. Restraint of Fgf8 signaling by retinoic acid signaling is required for proper heart and forelimb formation. Dev Biol. 2011;358:44-55 pubmed publisher
  47. Ma H, Blake T, Chitnis A, Liu P, Balla T. Crucial role of phosphatidylinositol 4-kinase IIIalpha in development of zebrafish pectoral fin is linked to phosphoinositide 3-kinase and FGF signaling. J Cell Sci. 2009;122:4303-10 pubmed publisher
    ..turn caused a prominent loss of the induction of one of the mitogen-activated protein kinase (MAPK) phosphatases, Mkp3, an essential intermediate in vertebrate limb development...
  48. Kawakami Y, Raya A, Raya R, Rodriguez Esteban C, Izpisua Belmonte J. Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo. Nature. 2005;435:165-71 pubmed
  49. Itou J, Kawakami H, Burgoyne T, Kawakami Y. Life-long preservation of the regenerative capacity in the fin and heart in zebrafish. Biol Open. 2012;1:739-46 pubmed publisher
    ..The expression of epicardial genes, such as wt1b and aldh1a2, in response to heart injury was comparable in two groups. Our results demonstrate that zebrafish preserve a life-long regenerative ability of the caudal fin and heart. ..
  50. Yano T, Abe G, Yokoyama H, Kawakami K, Tamura K. Mechanism of pectoral fin outgrowth in zebrafish development. Development. 2012;139:2916-25 pubmed publisher
  51. Simões M, Bensimon Brito A, Fonseca M, Farinho A, Valério F, Sousa S, et al. Denervation impairs regeneration of amputated zebrafish fins. BMC Dev Biol. 2014;14:49 pubmed publisher
  52. Varga M, Maegawa S, Weinberg E. Correct anteroposterior patterning of the zebrafish neurectoderm in the absence of the early dorsal organizer. BMC Dev Biol. 2011;11:26 pubmed publisher
    ..We also show that the zebrafish embryo can form a radial diffuse neural sheath in the absence of both BMP signaling and the early organizer. ..
  53. Rojas Muñoz A, Rajadhyksha S, Gilmour D, van Bebber F, Antos C, Rodriguez Esteban C, et al. ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration. Dev Biol. 2009;327:177-90 pubmed publisher