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The Nodal regulated dusp4 inhibits mesendoderm formation during zebrafish gastrulation

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  • State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

Received date: 2012-02-29

  Revised date: 2012-04-05

  Online published: 2012-09-25

Abstract

MAP kinase phosphatase-2 (MKP-2/DUSP4), a dual specificity protein phosphatase with tyrosine/serine/ threonine phosphatase activity, is associated with cellular proliferation and differentiation, but its functions during embryo development are unclear. To study the developmental function of dusp4, we first examined the spatiotemporal ex-pression pattern of this gene during zebrafish embryonic development by whole mount in situ hybridization. We found that dusp4 was maternally expressed since its transcripts were present from the one-cell to the 256-cell stages. At early gastrulation stages, dusp4 transcripts specifically distributed at margin region, where the mesendodermal cells were located. Furthermore, Nodal signal was crucial for dusp4 expression. The expression of dusp4 was obviously increased in Nodal ligand overexpressed embryos, while its expression was almost lost in the Nodal sig-nal-deficient MZoep mutants. In addition, dusp4 MO was also designed to knock down its expression in embryos. The mesendoderm formation was significantly increased in dusp4 morphants, but not obviously changed in dusp4 overexpressed embryos, suggesting that dusp4 is necessary, but not sufficient for the inhibitory of mesendoderm induction. Thus, our results indicate that Nodal regulated dusp4 plays a repressive role in mesendoderm induction.

Cite this article

LIU Zhao-Ting, WEI Shi, WANG Qiang . The Nodal regulated dusp4 inhibits mesendoderm formation during zebrafish gastrulation[J]. Hereditas(Beijing), 2012 , 34(9) : 1153 -1158 . DOI: 10.3724/SP.J.1005.2012.01153

References

[1] Schier AF. Nodal signaling in vertebrate development. Annu Rev Cell Dev Biol, 2003, 19: 589-621.
[2] Whitman M. Nodal signaling in early vertebrate embryos: themes and variations. Dev Cell, 2001, 1(5): 605-617.
[3] Tian T, Meng AM. Nodal signals pattern vertebrate em-bryos. Cell Mol Life Sci, 2006, 63(6): 672-685.
[4] Shen MM, Schier AF. The EGF-CFC gene family in vertebrate development. Trends Genet, 2000, 16(7): 303-309.
[5] Zhang JJ, Talbot WS, Schier AF. Positional cloning iden-tifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell, 1998, 92(2): 241-251.
[6] Gritsman K, Zhang JJ, Cheng S, Heckscher E, Talbot WS, Schier AF. The EGF-CFC protein one-eyed pinhead is es-sential for nodal signaling. Cell, 1999, 97(1): 121-132.
[7] Feldman B, Gates MA, Egan ES, Dougan ST, Rennebeck G, Sirotkin HI, Schier AF, Talbot WS. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature, 1998, 395(6698): 181-185.
[8] Massagué J. TGF-β signal transduction. Annu Rev Bio-chem, 1998, 67: 753-791.
[9] Massagué J, Seoane J, Wotton D. Smad transcription fac-tors. Genes Dev, 2005, 19(23): 2783-2810.
[10] Liu ZT, Lin XW, Cai ZP, Zhang ZQ, Han CS, Jia SJ, Meng AM, Wang Q. Global identification of SMAD2 target genes reveals a role for multiple co-regulatory factors in zebrafish early gastrulas. J Biol Chem, 2011, 286(32): 28520-28532.
[11] Patterson KI, Brummer T, O'Brien PM, Daly RJ. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J, 2009, 418(3): 475-489.
[12] Nunes-Xavier C, Roma-Mateo C, Ríos P, Tárrega C, Ce-judo-Marín R, Tabernero L, Pulido R. Dual-specificity MAP kinase phosphatases as targets of cancer treatment. Anticancer Agents Med Chem, 2011, 11(1): 109-132.
[13] Brondello JM, Brunet A, Pouysségur J, McKenzie FR. The dual specificity mitogen-activated protein kinase phos-phatase-1 and -2 are induced by the p42/p44MAPK cas-cade. J Biol Chem, 1997, 272(2): 1368-1376.
[14] Chen PL, Hutter D, Yang XL, Gorospe M, Davis RJ, Liu YS. Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phos-phatase catalytically. J Biol Chem, 2001, 276(31): 29440-29449.
[15] Robinson CJM, Sloss CM, Plevin R. Inactivation of JNK activity by mitogen-activated protein kinase phos-phatase-2 in EAhy926 endothelial cells is dependent upon agonist-specific JNK translocation to the nucleus. Cell Signal, 2001, 13(1): 29-41.
[16] Jeffrey KL, Camps M, Rommel C, Mackay CR. Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Dis-cov, 2007, 6(5): 391-403.
[17] Ramesh S, Qi XJ, Wildey GM, Robinson J, Molkentin J, Letterio J, Howe PH. TGFβ-mediated BIM expression and apoptosis are regulated through SMAD3-dependent expression of the MAPK phosphatase MKP2. EMBO Rep, 2008, 9(10): 990-997.
[18] Brown JL, Snir M, Noushmehr H, Kirby M, Hong SK, Elkahloun AG, Feldman B. Transcriptional profiling of endogenous germ layer precursor cells identifies dusp4 as an essential gene in zebrafish endoderm specification. Proc Natl Acad Sci USA, 2008, 105(34): 12337-12342.
[19] Bennett JT, Joubin K, Cheng S, Aanstad P, Herwig R, Clark M, Lehrach H, Schier AF. Nodal signaling activates differentiation genes during zebrafish gastrulation. Dev Biol, 2007, 304(2): 525-540.
[20] Tseng WF, Jang TH, Huang CB, Yuh CH. An evolutionarily conserved kernel of gata5, gata6, otx2 and prdm1a operates in the formation of endoderm in zebrafish. Dev Biol, 2011, 357(2): 541-557.
[21] Ao
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