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Gene Review

wnt8a  -  wingless-type MMTV integration site family...

Xenopus laevis

 
 
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High impact information on Xwnt-8

  • These observations implicate Frzb in axial patterning and support the concept that Frzb binds and inactivates Xwnt-8 during gastrulation, preventing inappropriate ventral signaling in developing dorsal tissues [1].
  • The phenotype can be rescued by the injection of beta-catenin mRNA and not by the injection of Xwnt-8 mRNA [2].
  • Expression cloning from a pool of gastrula cDNAs identified the Wnt family member Xwnt-8 as having dorsal axis-inducing activity in Xenopus embryos [3].
  • Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to differentiate in vitro as ventral mesoderm, no loss-of-function studies have demonstrated a requirement for Wnt signaling for the normal expression of mesodermal genes in the gastrula [4].
  • Mesoderm induction assays in Xenopus have implicated growth factors such as activin, Vg1, Xwnt-8, and noggin as important in directing the formation of dorsal mesoderm (Spemann's organizer) [5].
 

Biological context of Xwnt-8

  • Surprisingly, ectopic expression of Xwnt-8 in embryos causes a dorsoanterior-enhanced phenotype [6].
  • Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis [6].
  • Treatments known to decrease dorsal-anterior development in Xenopus laevis, UV irradiation during the first cell cycle or Xwnt-8 DNA injections into dorsal blastomeres, caused an increase in cardiac left-right reversals [7].
  • Expression of Xwnt-8 is observable during gastrulation, declines during neurulation, and is undetectable by the tadpole stage of development [8].
  • Finally, analysis of Xrx1 expression in embryos subjected to various treatments, or microinjected with different dorsalizing agents (noggin, Xwnt-8), suggests that vertical inductive signals leading to head morphogenesis are required to activate Xrx1 [9].
 

Anatomical context of Xwnt-8

  • In this paper we examine potential interactions between the bFGF and Xwnt-8 signaling pathways in the induction and dorsal-ventral patterning of mesoderm [10].
  • Injection of Xwnt-8 mRNA into 2-cell Xenopus embryos does not induce mesoderm formation in animal cap ectoderm isolated from these embryos at the blastula stage, but alters the response of this tissue to mesoderm induction by bFGF [10].
  • In contrast, injection of Xwnt-8 DNA into cardiac progenitor blastomeres did not result in left-right reversals, and dorsal-anterior development and notochord formation were normal [7].
  • Misexpression of Xwnt-8 during gastrulation produces an identical loss of forebrain [11].
  • Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus [12].
 

Associations of Xwnt-8 with chemical compounds

  • Embryos dorsoanteriorized by exposure to lithium exhibit greatly reduced levels of Xwnt-8 mRNA, supporting a correlation between Xwnt-8 expression and a ventral mesodermal cell fate [6].
  • Xwnt-3, Xwnt-4, Xwnt-5A, and Xwnt-8 demonstrate between 35 and 50% amino acid identity with X. laevis Wnt-1/int-1 and most cysteine residues are conserved [8].
  • Induction of Xlim1, 1A11, and, partially, Xbrachyury transcripts in the marginal zone was blocked by cycloheximide treatment through late blastula stages, whereas Goosecoid and Xwnt8 mRNAs were expressed in the absence of protein synthesis, indicating that these sets of markers are activated in vivo through different pathways [13].
 

Regulatory relationships of Xwnt-8

  • We also show that the spatial pattern of expression of these two genes along the animal-vegetal axis is similar in normal and in dissociated early gastrulae: goosecoid is mainly expressed in future mesoderm while the domain of expression of Xwnt-8 spans the mesoderm-endoderm boundary [14].
  • Xenopus wnt-8 (Xwnt-8) is one of the most potent Wnts to activate the WNT - beta-catenin - TCF signaling pathway [15].
 

Other interactions of Xwnt-8

  • Xwnt-8 injection produces complete secondary axes including head structures whereas activin and goosecoid injection produce partial secondary axes at high frequency that lack head structures anterior to the auditory vesicle and often lack notochord [16].
  • Co-expression of Xbra with Xwnt-8, in contrast, converts animal caps to muscle masses [17].
  • Analysis of markers in mutant embryos showed that genes involved in ventral-posterior patterning such as Xhox-3, Xwnt-8, and Xvent-1 were upregulated, confirming the posteriorized nature of the embryos [18].
  • Furthermore, Frzb blocked induction of MyoD, an action reported recently for a dominant-negative Xwnt-8 [1].
  • The results of these studies are consistent with the hypothesis that maternally derived signals from the Nieuwkoop center function to positively regulate expression of the homeo box gene goosecoid in Spemann organizer cells, leading to a subsequent repression of Xwnt-8 expression in these cells [12].
 

Analytical, diagnostic and therapeutic context of Xwnt-8

  • Whole-mount in situ hybridization showed that Xmsx-1, Xwnt-8, and XmyoD were expressed in overlapping areas, including the ventro-lateral marginal zone at mid-gastrula stage [19].

References

  1. Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. Wang, S., Krinks, M., Lin, K., Luyten, F.P., Moos, M. Cell (1997) [Pubmed]
  2. Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., McCrea, P., Kintner, C., Noro, C.Y., Wylie, C. Cell (1994) [Pubmed]
  3. Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center. Smith, W.C., Harland, R.M. Cell (1991) [Pubmed]
  4. Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos. Hoppler, S., Brown, J.D., Moon, R.T. Genes Dev. (1996) [Pubmed]
  5. Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. Watabe, T., Kim, S., Candia, A., Rothbächer, U., Hashimoto, C., Inoue, K., Cho, K.W. Genes Dev. (1995) [Pubmed]
  6. Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. Christian, J.L., McMahon, J.A., McMahon, A.P., Moon, R.T. Development (1991) [Pubmed]
  7. Linkage of cardiac left-right asymmetry and dorsal-anterior development in Xenopus. Danos, M.C., Yost, H.J. Development (1995) [Pubmed]
  8. Isolation of cDNAs partially encoding four Xenopus Wnt-1/int-1-related proteins and characterization of their transient expression during embryonic development. Christian, J.L., Gavin, B.J., McMahon, A.P., Moon, R.T. Dev. Biol. (1991) [Pubmed]
  9. Xrx1, a novel Xenopus homeobox gene expressed during eye and pineal gland development. Casarosa, S., Andreazzoli, M., Simeone, A., Barsacchi, G. Mech. Dev. (1997) [Pubmed]
  10. Xwnt-8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm. Christian, J.L., Olson, D.J., Moon, R.T. EMBO J. (1992) [Pubmed]
  11. Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos. Fredieu, J.R., Cui, Y., Maier, D., Danilchik, M.V., Christian, J.L. Dev. Biol. (1997) [Pubmed]
  12. Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus. Christian, J.L., Moon, R.T. Genes Dev. (1993) [Pubmed]
  13. The pregastrula establishment of gene expression pattern in Xenopus embryos: requirements for local cell interactions and for protein synthesis. Sokol, S.Y. Dev. Biol. (1994) [Pubmed]
  14. A role for cytoplasmic determinants in mesoderm patterning: cell-autonomous activation of the goosecoid and Xwnt-8 genes along the dorsoventral axis of early Xenopus embryos. Lemaire, P., Gurdon, J.B. Development (1994) [Pubmed]
  15. Expression and regulation of WNT8A and WNT8B mRNAs in human tumor cell lines: up-regulation of WNT8B mRNA by beta-estradiol in MCF-7 cells, and down-regulation of WNT8A and WNT8B mRNAs by retinoic acid in NT2 cells. Saitoh, T., Mine, T., Katoh, M. Int. J. Oncol. (2002) [Pubmed]
  16. Xenopus axis formation: induction of goosecoid by injected Xwnt-8 and activin mRNAs. Steinbeisser, H., De Robertis, E.M., Ku, M., Kessler, D.S., Melton, D.A. Development (1993) [Pubmed]
  17. Specification of mesodermal pattern in Xenopus laevis by interactions between Brachyury, noggin and Xwnt-8. Cunliffe, V., Smith, J.C. EMBO J. (1994) [Pubmed]
  18. The role of Xmsx-2 in the anterior-posterior patterning of the mesoderm in Xenopus laevis. Gong, S.G., Kiba, A. Differentiation (1999) [Pubmed]
  19. Xenopus msx-1 regulates dorso-ventral axis formation by suppressing the expression of organizer genes. Takeda, M., Saito, Y., Sekine, R., Onitsuka, I., Maeda, R., Maéno, M. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2000) [Pubmed]
 
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