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Gene Review

nog  -  noggin

Xenopus laevis

Synonyms: nog-A, nog1, noggin-1
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High impact information on nog-A


Biological context of nog-A

  • To investigate this issue, we identified a 2066 bp Xenopus noggin 5' flanking sequence which recapitulates the roof-plate expression of endogenous gene in transgenic frog tadpoles and we further mapped the roof-plate enhancer to a sequence as short as 79 bp [3].
  • The results suggest that follistatin acts as an organizer factor in early amphibian embryogenesis by inhibiting BMP activities by a different mechanism from that used by chordin and noggin [4].
  • Neurectoderm-specific gene expression was observed, however, in ectoderm overexpressing both noggin and MKP-1 [5].
  • In order to identify factors involved in posteriorization of the central nervous system, we undertook a functional screen in Xenopus animal cap explants which involved coinjecting noggin RNA together with pools of RNA from a chick somite cDNA library [6].
  • We have identified two noggin genes in the tropical clawed frog, X. tropicalis, a diploid anuran which is being explored for its potential as a genetic model system for early vertebrate development [7].

Anatomical context of nog-A

  • Injection of noggin or chordin RNA into animal pole blastomeres effectively inhibited VBI development, while marginal zone injection had no effect [8].
  • Treatment of isolated ectoderm with SB 203580 led to expression of otx2, NCAM, and noggin [9].
  • This neural induction correlates with the expression of chordin and other BMP inhibitors-such as noggin, follistatin, and Xnr3-at the blastula stage, and requires beta-Catenin signaling [10].
  • Analysis of explants overexpressing Xdsh at the gastrula stage revealed activation of several organizer-specific genes which have been implicated in determination of neural tissue (Xotx2, noggin, chordin and follistatin) [11].
  • The ability of chd, as well as that of noggin, to induce endoderm in animal cap explants is repressed by the ventralizing factor BMP-4 [12].

Associations of nog-A with chemical compounds

  • In addition, although dorsal mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and produce normal levels of the anterior neural inducing molecules noggin and chordin, they show a greatly reduced capacity to induce anterior neural tissue in conjugated ectoderm [13].

Regulatory relationships of nog-A

  • Endogenous BMP-4 transcripts are downregulated in ventral marginal zone explants dorsalized by noggin, in contrast to untreated explants [14].
  • Conversely, earlier in development, chordin can induce an ectopic primitive streak much more effectively than noggin, while neither BMP antagonist can induce neural tissue from extraembryonic epiblast [15].

Other interactions of nog-A

  • We found that BMP inhibition with cm-BMP7 mRNA had no rescuing effects on VegT(-) embryos, while cm-BMP7 and noggin mRNA caused a complete rescue of the trunk, but not of the anterior pattern in beta-catenin(-) embryos [16].
  • 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 [14].
  • Activation of XAG-2 transcription is observed in response to organizer-secreted molecules including the noggin, chordin, follistatin and cerberus gene products [17].
  • A loss-of-function study using the Xmsx-1/VP-16 fusion construct indicated that neural tissue formation was directly induced by the injection of fusion ribonucleic acid, although the expression of neural cell adhesion molecule (N-CAM) in the cap was less than that in the cap injected with tBR or noggin [18].
  • XBF-2 lies downstream of the BMP antagonists noggin, cerberus, and gremlin since ectodermal explants expressing these molecules exhibit strong expression of XBF-2 [19].

Analytical, diagnostic and therapeutic context of nog-A

  • Xmsx-1 antagonizes the dorsal expression of noggin and cerberus, as revealed by in situ hybridization and reverse transcription-polymerase chain reaction assays [18].
  • If noggin expression is induced followed by partial amputation of the tail, then wound closure and the formation of the neural ampulla occur normally but outgrowth of the regeneration bud is inhibited [20].


  1. Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Smith, W.C., Harland, R.M. Cell (1992) [Pubmed]
  2. Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm. Smith, W.C., Knecht, A.K., Wu, M., Harland, R.M. Nature (1993) [Pubmed]
  3. The Xenopus noggin promoter drives roof-plate specific transcription. Geng, X., Xiao, L., Tao, Q., Hu, R., Rupp, R.A., Ding, X. Neuroreport (2003) [Pubmed]
  4. Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. Iemura, S., Yamamoto, T.S., Takagi, C., Uchiyama, H., Natsume, T., Shimasaki, S., Sugino, H., Ueno, N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Mitogen-activated protein kinase and neural specification in Xenopus. Uzgare, A.R., Uzman, J.A., El-Hodiri, H.M., Sater, A.K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  6. The Wnt/beta-catenin pathway posteriorizes neural tissue in Xenopus by an indirect mechanism requiring FGF signalling. Domingos, P.M., Itasaki, N., Jones, C.M., Mercurio, S., Sargent, M.G., Smith, J.C., Krumlauf, R. Dev. Biol. (2001) [Pubmed]
  7. Expression of Xenopus tropicalis noggin1 and noggin2 in early development: two noggin genes in a tetrapod. Fletcher, R.B., Watson, A.L., Harland, R.M. Gene Expr. Patterns (2004) [Pubmed]
  8. Spatial and temporal properties of ventral blood island induction in Xenopus laevis. Kumano, G., Belluzzi, L., Smith, W.C. Development (1999) [Pubmed]
  9. 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]
  10. Neural induction in the absence of mesoderm: beta-catenin-dependent expression of secreted BMP antagonists at the blastula stage in Xenopus. Wessely, O., Agius, E., Oelgeschläger, M., Pera, E.M., De Robertis, E.M. Dev. Biol. (2001) [Pubmed]
  11. Graded amounts of Xenopus dishevelled specify discrete anteroposterior cell fates in prospective ectoderm. Itoh, K., Sokol, S.Y. Mech. Dev. (1997) [Pubmed]
  12. Endoderm induction by the organizer-secreted factors chordin and noggin in Xenopus animal caps. Sasai, Y., Lu, B., Piccolo, S., De Robertis, E.M. EMBO J. (1996) [Pubmed]
  13. 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]
  14. 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]
  15. Mesoderm patterning and somite formation during node regression: differential effects of chordin and noggin. Streit, A., Stern, C.D. Mech. Dev. (1999) [Pubmed]
  16. The roles of three signaling pathways in the formation and function of the Spemann Organizer. Xanthos, J.B., Kofron, M., Tao, Q., Schaible, K., Wylie, C., Heasman, J. Development (2002) [Pubmed]
  17. Anterior specification of embryonic ectoderm: the role of the Xenopus cement gland-specific gene XAG-2. Aberger, F., Weidinger, G., Grunz, H., Richter, K. Mech. Dev. (1998) [Pubmed]
  18. Involvement of BMP-4/msx-1 and FGF pathways in neural induction in the Xenopus embryo. Ishimura, A., Maeda, R., Takeda, M., Kikkawa, M., Daar, I.O., Maéno, M. Dev. Growth Differ. (2000) [Pubmed]
  19. XBF-2 is a transcriptional repressor that converts ectoderm into neural tissue. Mariani, F.V., Harland, R.M. Development (1998) [Pubmed]
  20. Temporal requirement for bone morphogenetic proteins in regeneration of the tail and limb of Xenopus tadpoles. Beck, C.W., Christen, B., Barker, D., Slack, J.M. Mech. Dev. (2006) [Pubmed]
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