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Noggin inhibits TGF-β signal transduction by binding to TGF-β family ligands and preventing them from binding to their corresponding receptors. Noggin plays a key role in neural induction by inhibiting BMP4, along with other TGF-β signaling inhibitors such as chordin and follistatin. Mouse knockout experiments have demonstrated that noggin also plays a crucial role in learning, cognition, bone development, joint formation, and neural tube fusion.
Genomics[edit | edit source]
The amino acid sequence of human noggin is highly homologous to that of Xenopus, rat and mouse.
Molecular biology[edit | edit source]
The secreted polypeptide noggin, encoded by the NOG gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, noggin may have a principal role in creating morphogenic gradients. Noggin appears to have pleiotropic effect, both early in development as well as in later stages. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation.
Clinical[edit | edit source]
Recently, several heterozygous missense human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) have been identified; both SYM1 and SYNS1 have multiple joint fusion as their principal feature, and map to the same region on chromosome 17 (17q22) as NOG. These mutations indicate functional haploinsufficiency where the homozygous forms are embryonically lethal.
All these NOG mutations have altered evolutionarily conserved amino acid residues.
Discovery[edit | edit source]
Noggin was discovered in the laboratory of Richard M. Harland and William C. Smith at the University of California, Berkeley because of its ability to induce secondary axis formation in frog embryos.
References[edit | edit source]
- Entrez Gene: NOG noggin.
- Phys Ed: Your Brain on Exercise. http://well.blogs.nytimes.com/2010/07/07/your-brain-on-exercise/?src=me&ref=general
- BMP Signaling Mediates Effects of Exercise on Hippocampal Neurogenesis and Cognition in Mice. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759555/
- Krause C, Guzman A, Knaus P (April 2011). Noggin. Int. J. Biochem. Cell Biol. 43 (4): 478–81.
- Valenzuela DM, Economides AN, Rojas E, Lamb TM, Nuñez L, Jones P, Lp NY, Espinosa R 3rd, Brannan CI, Gilbert DJ, Copeland NG, Jenkins NA, Le Beau MM, Harland RM, Yancopoulos GD (September 1995). Identification of mammalian noggin and its expression in the adult nervous system. J. Neurosci. 15 (9): 6077–84.
Further reading[edit | edit source]
- Polymeropoulos MH, Poush J, Rubenstein JR, Francomano CA (1995). Localization of the gene (SYM1) for proximal symphalangism to human chromosome 17q21-q22.. Genomics 27 (2): 225–9.
- Valenzuela DM, Economides AN, Rojas E, et al. (1995). Identification of mammalian noggin and its expression in the adult nervous system.. J. Neurosci. 15 (9): 6077–84.
- McMahon JA, Takada S, Zimmerman LB, et al. (1998). Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite.. Genes Dev. 12 (10): 1438–52.
- Brunet LJ, McMahon JA, McMahon AP, Harland RM (1998). Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton.. Science 280 (5368): 1455–7.
- Krakow D, Reinker K, Powell B, et al. (1998). Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21-22.. Am. J. Hum. Genet. 63 (1): 120–4.
- Smith WC (1999). TGF beta inhibitors. New and unexpected requirements in vertebrate development.. Trends Genet. 15 (1): 3–5.
- Gong Y, Krakow D, Marcelino J, et al. (1999). Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis.. Nat. Genet. 21 (3): 302–4.
- Li W, LoTurco JJ (2000). Noggin is a negative regulator of neuronal differentiation in developing neocortex.. Dev. Neurosci. 22 (1-2): 68–73.
- Dixon ME, Armstrong P, Stevens DB, Bamshad M (2002). Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism.. Genet. Med. 3 (5): 349–53.
- Marcelino J, Sciortino CM, Romero MF, et al. (2001). Human disease-causing NOG missense mutations: effects on noggin secretion, dimer formation, and bone morphogenetic protein binding.. Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11353–8.
- Beck HN, Drahushuk K, Jacoby DB, et al. (2003). Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured sympathetic neurons.. BMC neuroscience 2: 12.
- Paine-Saunders S, Viviano BL, Economides AN, Saunders S (2002). Heparan sulfate proteoglycans retain Noggin at the cell surface: a potential mechanism for shaping bone morphogenetic protein gradients.. J. Biol. Chem. 277 (3): 2089–96.
- Takahashi T, Takahashi I, Komatsu M, et al. (2002). Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome.. Clin. Genet. 60 (6): 447–51.
- Mangino M, Flex E, Digilio MC, et al. (2002). Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism.. Hum. Mutat. 19 (3): 308.
- Brown DJ, Kim TB, Petty EM, et al. (2002). Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding noggin.. Am. J. Hum. Genet. 71 (3): 618–24.
- Hall AK, Burke RM, Anand M, Dinsio KJ (2002). Activin and bone morphogenetic proteins are present in perinatal sensory neuron target tissues that induce neuropeptides.. J. Neurobiol. 52 (1): 52–60.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903.
- Groppe J, Greenwald J, Wiater E, et al. (2003). Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.. Nature 420 (6916): 636–42.
- Brown DJ, Kim TB, Petty EM, et al. (2003). Characterization of a stapes ankylosis family with a NOG mutation.. Otol. Neurotol. 24 (2): 210–5.
[edit | edit source]
- BMPedia - the Bone Morphogenetic Protein Wiki
- Noggin publications, gene expression data, sequences and interactants from Xenbase
- Template:UCSC genome browser
- Template:UCSC gene details
Cell signaling: TGF beta signaling pathway
|TGF beta superfamily of ligands||
TGF beta family (TGF-β1, TGF-β2, TGF-β3)
|TGF beta receptors|