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Gene Review

Nog  -  noggin

Mus musculus

Synonyms: Noggin
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Disease relevance of Nog


High impact information on Nog


Chemical compound and disease context of Nog


Biological context of Nog

  • To elucidate roles of Chrd and Nog that are masked by the severe phenotype and early lethality of the double null, we have characterized embryos of the genotype Chrd(-/-);Nog(+/-) [11].
  • As the telencephalic vesicle closed, Nog expression was expanded and BMP activity reduced, potentially leading to FGF8 upregulation [12].
  • Mice mutant for either Nog or Chd have only mild mandibular defects; however, pups of the genotype Chd(-/-);Nog(+/-) exhibit a range of mandibular truncation phenotypes, from normal to agnathia [13].
  • Anagen development is accompanied by down-regulation of the BMP4 and increased noggin mRNA in the HF [14].
  • To obtain tissue-specific inactivation, Noggin gene (Nog) was overexpressed in cartilage under the control of a2(XI) collagen gene (Collla2) promoter/enhancer sequences [15].

Anatomical context of Nog


Associations of Nog with chemical compounds

  • In this study, we investigated expression of noggin in murine pluripotent mesodermal cell line, C1 [19].
  • In the present study, we generated transgenic mice carrying cDNA for noggin, an endogenous inhibitor of BMPs, driven by the podocyte-specific promoter nephrin [20].
  • In a sharp contrast, when the C1 cells were induced to differentiate into osteoblastic cells by the treatment with beta glycerophosphate (betaGP) and ascorbic acid (AA), noggin mRNA expression remained to be barely detectable [19].
  • Cotreatment with the BMP antagonist noggin or the NADPH oxidase inhibitor apocynin completely blocked the BMP4 effect [21].
  • Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation [21].

Regulatory relationships of Nog

  • In mandibular explants, ectopic BMP4 rapidly induces expression of both Chd and Nog, consistent with results obtained in vivo with mutant embryos [13].
  • In contrast, TrkC-expressing neurons decreased in both plexuses of postnatal noggin-overexpressing animals, again an effect detectable at E18 [22].
  • To determine the physiological significance of these observations, the BMP antagonist noggin was overexpressed in the developing ENS of transgenic mice under the control of the neuron-specific enolase promoter [22].
  • MATERIALS AND METHODS: We generated transgenic mice that express BMP4 or noggin in bone under the control of the 2.3-kb alpha1(I) collagen chain gene (Col1a1) promoter, and analyzed their bone phenotype [23].
  • FGF18 represses noggin expression and is induced by calcineurin [24].

Other interactions of Nog

  • When endogenous BMP signaling is inhibited by noggin, robust Fgf8 expression appears ectopically in the cortical primordium [12].
  • The BMP antagonists cerberus-like and noggin do not interact during mouse forebrain development [25].
  • Misexpression of HtrA1 near the developing chick eye led to suppression of eye development that was indistinguishable from the effects of noggin [26].
  • Consistent with the endogenous markers, pOBCol3.6GFP and pOBCOL2.3GFP transgene activity was completely inhibited by continuous addition of FGF2, while noggin showed partial inhibition of pOBCol3.6GFP and complete inhibition of the pOBCol2.3GFP transgene [27].
  • By contrast, the expression domains of Indian hedgehog (Ihh), patched, and noggin become restricted as decidualization proceeds [28].

Analytical, diagnostic and therapeutic context of Nog


  1. Modulation of BMP signaling by noggin is required for induction of the secondary (nontylotrich) hair follicles. Botchkarev, V.A., Botchkareva, N.V., Sharov, A.A., Funa, K., Huber, O., Gilchrest, B.A. J. Invest. Dermatol. (2002) [Pubmed]
  2. The BMP antagonist noggin regulates cranial suture fusion. Warren, S.M., Brunet, L.J., Harland, R.M., Economides, A.N., Longaker, M.T. Nature (2003) [Pubmed]
  3. Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex. Winkler, D.G., Yu, C., Geoghegan, J.C., Ojala, E.W., Skonier, J.E., Shpektor, D., Sutherland, M.K., Latham, J.A. J. Biol. Chem. (2004) [Pubmed]
  4. Misexpression of noggin leads to septal defects in the outflow tract of the chick heart. Allen, S.P., Bogardi, J.P., Barlow, A.J., Mir, S.A., Qayyum, S.R., Verbeek, F.J., Anderson, R.H., Francis-West, P.H., Brown, N.A., Richardson, M.K. Dev. Biol. (2001) [Pubmed]
  5. Function of BMPs in the apical ectoderm of the developing mouse limb. Wang, C.K., Omi, M., Ferrari, D., Cheng, H.C., Lizarraga, G., Chin, H.J., Upholt, W.B., Dealy, C.N., Kosher, R.A. Dev. Biol. (2004) [Pubmed]
  6. Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Gong, Y., Krakow, D., Marcelino, J., Wilkin, D., Chitayat, D., Babul-Hirji, R., Hudgins, L., Cremers, C.W., Cremers, F.P., Brunner, H.G., Reinker, K., Rimoin, D.L., Cohn, D.H., Goodman, F.R., Reardon, W., Patton, M., Francomano, C.A., Warman, M.L. Nat. Genet. (1999) [Pubmed]
  7. The organizer factors Chordin and Noggin are required for mouse forebrain development. Bachiller, D., Klingensmith, J., Kemp, C., Belo, J.A., Anderson, R.M., May, S.R., McMahon, J.A., McMahon, A.P., Harland, R.M., Rossant, J., De Robertis, E.M. Nature (2000) [Pubmed]
  8. Dkk1 and noggin cooperate in mammalian head induction. del Barco Barrantes, I., Davidson, G., Gröne, H.J., Westphal, H., Niehrs, C. Genes Dev. (2003) [Pubmed]
  9. Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. Wu, X.B., Li, Y., Schneider, A., Yu, W., Rajendren, G., Iqbal, J., Yamamoto, M., Alam, M., Brunet, L.J., Blair, H.C., Zaidi, M., Abe, E. J. Clin. Invest. (2003) [Pubmed]
  10. Noggin gene delivery inhibits cementoblast-induced mineralization. Jin, Q.M., Zhao, M., Economides, A.N., Somerman, M.J., Giannobile, W.V. Connect. Tissue Res. (2004) [Pubmed]
  11. Chordin and noggin promote organizing centers of forebrain development in the mouse. Anderson, R.M., Lawrence, A.R., Stottmann, R.W., Bachiller, D., Klingensmith, J. Development (2002) [Pubmed]
  12. Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex. Shimogori, T., Banuchi, V., Ng, H.Y., Strauss, J.B., Grove, E.A. Development (2004) [Pubmed]
  13. The BMP antagonists Chordin and Noggin have essential but redundant roles in mouse mandibular outgrowth. Stottmann, R.W., Anderson, R.M., Klingensmith, J. Dev. Biol. (2001) [Pubmed]
  14. Noggin is required for induction of the hair follicle growth phase in postnatal skin. Botchkarev, V.A., Botchkareva, N.V., Nakamura, M., Huber, O., Funa, K., Lauster, R., Paus, R., Gilchrest, B.A. FASEB J. (2001) [Pubmed]
  15. Bone morphogenetic protein signals are required for cartilage formation and differently regulate joint development during skeletogenesis. Tsumaki, N., Nakase, T., Miyaji, T., Kakiuchi, M., Kimura, T., Ochi, T., Yoshikawa, H. J. Bone Miner. Res. (2002) [Pubmed]
  16. Opposing effects of bone morphogenetic proteins on neuron production and survival in the olfactory receptor neuron lineage. Shou, J., Murray, R.C., Rim, P.C., Calof, A.L. Development (2000) [Pubmed]
  17. Indian hedgehog as a progesterone-responsive factor mediating epithelial-mesenchymal interactions in the mouse uterus. Matsumoto, H., Zhao, X., Das, S.K., Hogan, B.L., Dey, S.K. Dev. Biol. (2002) [Pubmed]
  18. Bone morphogenetic protein-2 can mediate myocardial regulation of atrioventricular cushion mesenchymal cell formation in mice. Sugi, Y., Yamamura, H., Okagawa, H., Markwald, R.R. Dev. Biol. (2004) [Pubmed]
  19. Noggin expression in a mesodermal pluripotent cell line C1 and its regulation by BMP. Nifuji, A., Kellermann, O., Noda, M. J. Cell. Biochem. (1999) [Pubmed]
  20. Inhibition of endogenous BMP in the glomerulus leads to mesangial matrix expansion. Miyazaki, Y., Ueda, H., Yokoo, T., Utsunomiya, Y., Kawamura, T., Matsusaka, T., Ichikawa, I., Hosoya, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation. Miriyala, S., Gongora Nieto, M.C., Mingone, C., Smith, D., Dikalov, S., Harrison, D.G., Jo, H. Circulation (2006) [Pubmed]
  22. Bone morphogenetic protein-2 and -4 limit the number of enteric neurons but promote development of a TrkC-expressing neurotrophin-3-dependent subset. Chalazonitis, A., D'Autréaux, F., Guha, U., Pham, T.D., Faure, C., Chen, J.J., Roman, D., Kan, L., Rothman, T.P., Kessler, J.A., Gershon, M.D. J. Neurosci. (2004) [Pubmed]
  23. Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Okamoto, M., Murai, J., Yoshikawa, H., Tsumaki, N. J. Bone Miner. Res. (2006) [Pubmed]
  24. FGF18 represses noggin expression and is induced by calcineurin. Reinhold, M.I., Abe, M., Kapadia, R.M., Liao, Z., Naski, M.C. J. Biol. Chem. (2004) [Pubmed]
  25. The BMP antagonists cerberus-like and noggin do not interact during mouse forebrain development. Borges, A.C., Marques, S., Belo, J.A. Int. J. Dev. Biol. (2001) [Pubmed]
  26. HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins. Oka, C., Tsujimoto, R., Kajikawa, M., Koshiba-Takeuchi, K., Ina, J., Yano, M., Tsuchiya, A., Ueta, Y., Soma, A., Kanda, H., Matsumoto, M., Kawaichi, M. Development (2004) [Pubmed]
  27. Stage specific inhibition of osteoblast lineage differentiation by FGF2 and noggin. Kalajzic, I., Kalajzic, Z., Hurley, M.M., Lichtler, A.C., Rowe, D.W. J. Cell. Biochem. (2003) [Pubmed]
  28. Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors. Paria, B.C., Ma, W., Tan, J., Raja, S., Das, S.K., Dey, S.K., Hogan, B.L. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  29. BMP4 promotes chondrocyte proliferation and hypertrophy in the endochondral cranial base. Shum, L., Wang, X., Kane, A.A., Nuckolls, G.H. Int. J. Dev. Biol. (2003) [Pubmed]
  30. Coordinated expression of noggin and bone morphogenetic proteins (BMPs) during early skeletogenesis and induction of noggin expression by BMP-7. Nifuji, A., Noda, M. J. Bone Miner. Res. (1999) [Pubmed]
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