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Gene Review

bmp4-b  -  bone morphogenetic protein 4

Xenopus laevis

Synonyms: XBMP-4, bmp2b, bmp2b1, bmp4, ofc11, ...
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High impact information on Bmp4

  • The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4 [1].
  • Moreover, the dominant-negative activin receptor, which stimulates neuralization when expressed in the embryo, blocks Bmp-4 in our assay [2].
  • Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm [3].
  • Endogenous BMP-4 transcripts are downregulated in ventral marginal zone explants dorsalized by noggin, in contrast to untreated explants [4].
  • Ectopic expression of BMP-4 RNA reduces goosecoid and forkhead-1 transcription in whole embryos and in activin-treated animal cap explants [4].

Biological context of Bmp4

  • The erythroid transcription factor GATA-1 functions downstream of the BMP-4 signaling pathway and mediates BMP-4-induced erythropoiesis [5].
  • Six3 functions in anterior neural plate specification by promoting cell proliferation and inhibiting Bmp4 expression [6].
  • Thus, Xiro1 is probably a mediator of the known downregulation of Bmp4 by Wnt signaling [7].
  • However, Six3 can still expand the neural plate in the presence of cell cycle inhibitors and we show that this is likely to be due to its ability to repress the expression of Bmp4 in ectoderm adjacent to the anterior neural plate [6].
  • As a consequence of the suppression of dorsal mesoderm gene expression, bone morphogenetic factor-4 (Bmp-4), a potent inducer of ventral mesoderm, is activated in the Organizer [8].

Anatomical context of Bmp4


Associations of Bmp4 with chemical compounds

  • MAPK activity was reduced in ectoderm expressing a constitutively active BMP-4 receptor, or ectoderm treated with BMP-4 protein in the presence or absence of cycloheximide [11].
  • In addition, we found that the connective tissue-specific expression of BMP-4 mRNA is up-regulated by sonic hedgehog (Shh), whose epithelium-specific expression is directly induced by TH [13].

Other interactions of Bmp4

  • Triple Bmp2/Bmp4/Bmp7 depletion further compromised trunk development but did not eliminate dorsoventral patterning [9].
  • Bmp4 knockdown was sufficient to rescue the ventralizing effects caused by loss of Chordin activity [9].
  • Ventral marginal zone explants ectopically expressing BMP-4 form less muscle when treated with soluble noggin protein or when juxtaposed to a normal Spemann organizer in comparison to control explants [4].
  • Furthermore, neuralization elicited by noggin or 3m, a LIM domain mutant of Xlim-1, was substantially inhibited by co-injection of BMP4 mRNA [14].
  • Here we provide evidence that PV.1 also functions downstream of BMP4 in the patterning of ectoderm, specifying epidermal and suppressing neural gene expression [15].

Analytical, diagnostic and therapeutic context of Bmp4


  1. The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Zimmerman, L.B., De Jesús-Escobar, J.M., Harland, R.M. Cell (1996) [Pubmed]
  2. Induction of epidermis and inhibition of neural fate by Bmp-4. Wilson, P.A., Hemmati-Brivanlou, A. Nature (1995) [Pubmed]
  3. Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development. Baker, J.C., Beddington, R.S., Harland, R.M. Genes Dev. (1999) [Pubmed]
  4. Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopus development. Re'em-Kalma, Y., Lamb, T., Frank, D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. Differential regulation of neurogenesis by the two Xenopus GATA-1 genes. Xu, R.H., Kim, J., Taira, M., Lin, J.J., Zhang, C.H., Sredni, D., Evans, T., Kung, H.F. Mol. Cell. Biol. (1997) [Pubmed]
  6. Six3 functions in anterior neural plate specification by promoting cell proliferation and inhibiting Bmp4 expression. Gestri, G., Carl, M., Appolloni, I., Wilson, S.W., Barsacchi, G., Andreazzoli, M. Development (2005) [Pubmed]
  7. The Wnt-activated Xiro1 gene encodes a repressor that is essential for neural development and downregulates Bmp4. Gómez-Skarmeta, J., de La Calle-Mustienes, E., Modolell, J. Development (2001) [Pubmed]
  8. XIPOU 2 is a potential regulator of Spemann's Organizer. Witta, S.E., Sato, S.M. Development (1997) [Pubmed]
  9. Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos. Reversade, B., Kuroda, H., Lee, H., Mays, A., De Robertis, E.M. Development (2005) [Pubmed]
  10. Follistatin and noggin are excluded from the zebrafish organizer. Bauer, H., Meier, A., Hild, M., Stachel, S., Economides, A., Hazelett, D., Harland, R.M., Hammerschmidt, M. Dev. Biol. (1998) [Pubmed]
  11. Regulation of MAP kinase by the BMP-4/TAK1 pathway in Xenopus ectoderm. Goswami, M., Uzgare, A.R., Sater, A.K. Dev. Biol. (2001) [Pubmed]
  12. Interplay between Notch signaling and the homeoprotein Xiro1 is required for neural crest induction in Xenopus embryos. Glavic, A., Silva, F., Aybar, M.J., Bastidas, F., Mayor, R. Development (2004) [Pubmed]
  13. Shh/BMP-4 signaling pathway is essential for intestinal epithelial development during Xenopus larval-to-adult remodeling. Ishizuya-Oka, A., Hasebe, T., Shimizu, K., Suzuki, K., Ueda, S. Dev. Dyn. (2006) [Pubmed]
  14. A dominant negative bone morphogenetic protein 4 receptor causes neuralization in Xenopus ectoderm. Xu, R.H., Kim, J., Taira, M., Zhan, S., Sredni, D., Kung, H.F. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  15. The homeobox gene PV.1 mediates specification of the prospective neural ectoderm in Xenopus embryos. Ault, K.T., Xu, R.H., Kung, H.F., Jamrich, M. Dev. Biol. (1997) [Pubmed]
  16. Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1. Wilson, P.A., Lagna, G., Suzuki, A., Hemmati-Brivanlou, A. Development (1997) [Pubmed]
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