NOG (gen)

NOG (gen)
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1M4U
Identifikatori
Aliasi	NOG
Vanjski ID-jevi	OMIM: 602991 MGI: 104327 HomoloGene: 3979 GeneCards: NOG
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	56,595,611 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	89,193,158 bp
Ontologija gena
Molekularna funkcija	• protein homodimerization activity; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:0019974 cytokine binding;
Ćelijska komponenta	• extracellular region; • Vanćelijsko;
Biološki proces	• positive regulation of glomerulus development; • pattern specification process; • axial mesoderm development; • skeletal system development; • Ćelijska diferencijacija; • ureteric bud development; • negative regulation of astrocyte differentiation; • pituitary gland development; • positive regulation of branching involved in ureteric bud morphogenesis; • lung morphogenesis; • negative regulation of cartilage development; • somatic stem cell population maintenance; • fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation; • positive regulation of epithelial cell proliferation; • negative regulation of cytokine activity; • neural plate morphogenesis; • negative regulation of cell differentiation; • anatomical structure formation involved in morphogenesis; • mesoderm formation; • negative regulation of apoptotic signaling pathway; • embryonic digit morphogenesis; • cellular response to BMP stimulus; • Zarastanje rana; • in utero embryonic development; • BMP signaling pathway; • negative regulation of gene expression; • somite development; • negative regulation of osteoblast differentiation; • embryonic skeletal system development; • nervous system development; • axon guidance; • negative regulation of BMP signaling pathway; • regulation of BMP signaling pathway; • multicellular organism development; • prostatic bud formation; • limb development; • central nervous system development; • cartilage development; • neural tube closure; • brain development; • negative regulation of cell migration; • notochord morphogenesis; • cell differentiation in hindbrain; • mesenchymal cell differentiation; • regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation; • neural tube development; • spinal cord development; • ureteric bud formation; • epithelial to mesenchymal transition; • middle ear morphogenesis; • embryonic skeletal joint morphogenesis; • urogenital system development; • endoderm formation; • negative regulation of cardiac muscle cell proliferation; • motor neuron axon guidance; • dorsal/ventral pattern formation; • negative regulation of canonical Wnt signaling pathway; • face morphogenesis; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • GO:1901227 negative regulation of transcription by RNA polymerase II; • osteoblast differentiation; • membranous septum morphogenesis; • outflow tract morphogenesis; • endocardial cushion morphogenesis; • ventricular compact myocardium morphogenesis; • endoderm development; • GO:1901313 positive regulation of gene expression; • atrial cardiac muscle tissue morphogenesis; • negative regulation of pathway-restricted SMAD protein phosphorylation; • ventricular septum morphogenesis; • BMP signaling pathway involved in heart development; • heart trabecula morphogenesis; • pharyngeal arch artery morphogenesis; • negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation;
	Izvori:Amigo / QuickGO
Ortolozi
	9241
	18121
	ENSG00000183691
	ENSMUSG00000048616
	Q13253
	P97466
	NM_005450
	NM_008711
	NP_005441
	NP_032737
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Nogin, poznat i kao NOG, je protein koji je uključen u razvoj mnogih tjelesnih tkiva, uključujući nervno, mišiće i kosti. Kod ljudi kodiran je genom i NOG.^[5] Aminokiselinska sekvenca ljudskog nogina vrlo je homologna odgovarajućojsekvenci pacova, miša i kandžaste žabe (rod vodenih žaba).

Nogin je inhibitor nekoliko morfogenetskih proteina kostiju (BMP): inhibira najmanje BMP2, BMP4, BMP5, BMP6, BMP7, BMP13 i BMP14.^[6]

Ime proteina, što je slengovska riječ na engleskom jeziku za "glava", nastalo je u odnosu na njegovu sposobnost stvaranja embriona s velikim glavama kada su izloženi visokim koncentracijama.^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 232 aminokiseline, a molekulska težina 25.774 Da.^[8]

10	20	30	40	50
MERCPSLGVT	LYALVVVLGL	RATPAGGQHY	LHIRPAPSDN	LPLVDLIEHP
DPIFDPKEKD	LNETLLRSLL	GGHYDPGFMA	TSPPEDRPGG	GGGAAGGAED
LAELDQLLRQ	RPSGAMPSEI	KGLEFSEGLA	QGKKQRLSKK	LRRKLQMWLW
SQTFCPVLYA	WNDLGSRFWP	RYVKVGSCFS	KRSCSVPEGM	VCKPSKSVHL
TVLRWRCQRR	GGQRCGWIPI	QYPIISECKC	SC

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Funkcija

Nogin je signalna molekula koja igra važnu ulogu u podsticanju somitnih obrazaca embriona u razvoju.^[9] Otpušta se iz notohorde i regulira razvijajući morfogeni protein koštiju (BMP4).^[10] Odsustvo BMP4 utiče na obrasce nervne cijevi i somita s nervne ploče u embrionu u razvoju. Također uzrokuje stvaranje glave i drugih leđnih struktura.^[10]

Funkcija nogina potrebna je za ispravan razvoj živčanog sistema, somita i skeleta.^[10] Eksperimenti na miševima pokazali su da ima ulogu i u učenju, spoznaji^[11] razviju kostiju,^[12] i spajanju nervne cijevi.^[13] Heterozigotna misens mutacije u genu nogina može prouzrokovati deformacije kao što su fuzije zglobova i sindromi kao što je multipla sinostoza, sindrom (SYNS1) i proksimalni simfalangizam (SIM1).^[10] SYNS1 se razlikuje od SYM1, uzrokujući fuzije kukova i kičmenih pršljenova.^[10] Embrion može razviti i kraće kosti, propustiti bilo koji koštani element ili mu nedostajati više zglobnih dijelova.^[10]

Povećani nivoi nogina u plazmi zabilježeni su kod gojaznih miševa i kod pacijenata s BMI|indeksom tjelesne mase]] preko 27.^[14] Pored toga, pokazano je da iscrpljivanje nogina u masnom tkivu dovodi do gojaznosti.^[15]

Mehanizam djelovanja

Izlučeni polipeptidni nogin, kodiran genom NOG, veže i inaktivira članove transformirajućeg faktora rasta beta (TGF-beta) proteinske signalne superporodice, kao što je morfogenetski protein kosti -4 (BMP4).

Difuzijom kroz vanćelijske matrice efikasnije od članova TGF-beta superfamilije, nogin može imati glavnu ulogu u stvaranju morfogenih gradijenata. Čini se da nogin ima plejotropne efekte, kako u ranom razvoju, tako i u kasnijim fazama.

Model nokauta

Studija modela nokaut-miša pratila je u kojoj je mjeri odsustvo nogina uticalo na razvoj embriona. Fokus studije bio je na formiranju uha i njegovoj ulozi u provodnom gubitku sluha. Unutrašnje uho pretrpjelo je višestruke deformacije. zahvatajući pužnjični kanal, polukružne kanale i dijelove očne jabučice. Pokazalo se da je i noginovo učešće u malformacijama indirektno, preko interakcijed s notokordom i nervnom osovinom. Prevrtanje notohorda i dezorijentacija tjelesne osi rezultira kaudalnim pomakom stražnjeg mozga u embrionskom planu tijela. Glavne signalne molekule iz rombomernih struktura zadnjeg mozga nisu mogli pravilno inducirati stvaranje unutrašnjeg uha. Ovo je odražavalo reguliranje BMP-a noginom kao glavnim izvorom deformacije, umjesto da nogin direktno utiče na razvoj unutrašnjeg uha.^[16]

Specifični modeli nokauta stvoreni su sistemom Cre-lox. Model koji nogin eksprimira konkretno u adipocitima omogućio je da se utvrdi da također ima ulogu u masnom tkivu: njegovo iscrpljivanje u adipocitima uzrokuje promjene u strukturi i smeđeg i bijelog masnog tkiva, zajedno sa disfunkcijama smeđeg (poremećena termogeneza i β-oksidacija) koja rezultira dramatičnim povećanjem tjelesne težine i postotka tjelesne masti što uzrokuje promjene u lipidnom profilu i jetri; efekti se razlikuju ovisno o spolu.

Klinički značaj

Noginski proteini imaju ulogu u izvođenju specijaliziranih ćelija specifičnih za klicni sloj. Stvaranje neuronskih tkiva, notohorda, folikula dlake i očnih struktura proizlazi iz ektodermmnog klicnog sloja. Noginska aktivnost u mezodermu ustupa mjesto formiranju hrskavice, rasta kostiju i mišića, a u endodermu uključen je u razvoj pluća.^[17]

Prisustvo nogina jako utječe na rani kraniofacijalni razvoj, u skladu sa njegovim višestrukim potrebama specifičnim za tkivo. Nogin utiče na stvaranje i rast nepca, donje vilice i lobanje, interakcijom sa stanama nervog grebena. Pokazalo se da miševi s nedostatkom NOG gena imaju izraslinu donje vilice i rascjep nepca. Sljedeća kraniofacijalna deformacija zbog odsutnosti nogina je provodni gubitak sluha, uzrokovan nekontroliranim izrastanjem i namotavanjem pužničnog kanala.^[18]

Nedavno je identificirano nekoliko heterozigotnih pogrešnih mutacija ljudskih NOG mutacija u nepovezanim porodicama sa proksimalnim simfalangizmom (SYM1) i sindromom multiplih sinostoza (SYNS1); i SYM1 i SYNS1 imaju glavno svojstvo višestruke fuzije zglobova i mapiraju se u isto područje na hromosomu 17 (17q22) kao NOG. Ove mutacije ukazuju na funkcionalnu haploinsuficijenciju gdje su homozigot ni oblici embriona smrtonosni.^[17]

Sve ove NOG mutacije promijenile su evolucijski konzervirane aminokiselinske ostatke.

Mutacije ovog gena povezane su s abnormalnostima srednjeg uha.^[19]

Otkriće

Nogin je prvobitno bio izoliran iz roda vodenih žaba Xenopus. Otkriće se temeljilo na sposobnosti organizma da obnovi normalnu leđno-trbušnu osovinu tijela u embrionima koji su vještački podvrgnuti ventilaciji ultraljubičastim tretmanima. Nogin je otkriven u laboratoriji Richarda M. Harlanda i Williama C. Smitha na Kalifornijskom univerzitetu, Berkeley, zbog ove sposobnosti da inducira stvaranje sekundarne osovine u embrionima žaba.^[20]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000183691 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000048616 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: NOG noggin".
^ Blázquez-Medela AM, Jumabay M, Boström KI (maj 2019). "Beyond the bone: Bone morphogenetic protein signaling in adipose tissue". Obesity Reviews. 20 (5): 648–658. doi:10.1111/obr.12822. PMC 6447448. PMID 30609449.
^ Oppenheimer SB (1995). "The Discovery of Noggin". The American Biology Teacher. 57 (5): 264–266. doi:10.2307/4449989. hdl:10211.2/1126. JSTOR 4449989.
^ "UniProt, Q13253". Pristupljeno 24. 6. 2021.
^ Hirsinger E, Duprez D, Jouve C, Malapert P, Cooke J, Pourquié O (novembar 1997). "Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning". Development. 124 (22): 4605–14. PMID 9409677.
^ ^a ^b ^c ^d ^e ^f Marcelino J, Sciortino CM, Romero MF, Ulatowski LM, Ballock RT, Economides AN, Eimon PM, Harland RM, Warman ML (septembar 2001). "Human disease-causing NOG missense mutations: effects on noggin secretion, dimer formation, and bone morphogenetic protein binding". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11353–8. doi:10.1073/pnas.201367598. PMC 58733. PMID 11562478.
^ Xu H, Huang W, Wang Y, Sun W, Tang J, Li D, Xu P, Guo L, Yin ZQ, Fan X (januar 2013). "The function of BMP4 during neurogenesis in the adult hippocampus in Alzheimer's disease". Ageing Research Reviews. 12 (1): 157–64. doi:10.1016/j.arr.2012.05.002. PMID 22698853. S2CID 46528212.
^ Potti TA, Petty EM, Lesperance MM (august 2011). "A comprehensive review of reported heritable noggin-associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG-related-symphalangism spectrum disorder (NOG-SSD)" (PDF). Human Mutation. 32 (8): 877–86. doi:10.1002/humu.21515. PMID 21538686. S2CID 205920339.
^ Liu A, Niswander LA (decembar 2005). "Bone morphogenetic protein signalling and vertebrate nervous system development". Nature Reviews. Neuroscience. 6 (12): 945–54. doi:10.1038/nrn1805. PMID 16340955. S2CID 1005572.
^ Sawant A, Chanda D, Isayeva T, Tsuladze G, Garvey WT, Ponnazhagan S (april 2012). "Noggin is novel inducer of mesenchymal stem cell adipogenesis: implications for bone health and obesity". The Journal of Biological Chemistry. 287 (15): 12241–9. doi:10.1074/jbc.m111.293613. PMC 3320975. PMID 22351751.
^ Blázquez-Medela AM, Jumabay M, Rajbhandari P, Sallam T, Guo Y, Yao J, Vergnes L, Reue K, Zhang L, Yao Y, Fogelman AM, Tontonoz P, Lusis AJ, Wu X, Boström KI (april 2019). "Noggin depletion in adipocytes promotes obesity in mice". Molecular Metabolism. 25: 50–63. doi:10.1016/j.molmet.2019.04.004. PMC 6600080. PMID 31027994.
^ Bok J, Brunet LJ, Howard O, Burton Q, Wu DK (novembar 2007). "Role of hindbrain in inner ear morphogenesis: analysis of Noggin knockout mice". Developmental Biology. 311 (1): 69–78. doi:10.1016/j.ydbio.2007.08.013. PMC 2215324. PMID 17900554.
^ ^a ^b Krause C, Guzman A, Knaus P (april 2011). "Noggin". The International Journal of Biochemistry & Cell Biology. 43 (4): 478–81. doi:10.1016/j.biocel.2011.01.007. PMID 21256973.
^ Masuda S, Namba K, Mutai H, Usui S, Miyanaga Y, Kaneko H, Matsunaga T (maj 2014). "A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss". Biochemical and Biophysical Research Communications. 447 (3): 496–502. doi:10.1016/j.bbrc.2014.04.015. PMID 24735539.
^ Lindquist NR, Appelbaum EN, Acharya A, Vrabec JT, Leal SM, Schrauwen I (2019) A start codon variant in NOG underlies symphalangism and ossicular chain malformations affecting both the incus and the stapes. Case Rep Genet 2019:2836263
^ Valenzuela DM, Economides AN, Rojas E, Lamb TM, Nuñez L, Jones P, Lp NY, Espinosa R, Brannan CI, Gilbert DJ (septembar 1995). "Identification of mammalian noggin and its expression in the adult nervous system". The Journal of Neuroscience. 15 (9): 6077–84. doi:10.1523/JNEUROSCI.15-09-06077.1995. PMC 6577675. PMID 7666191.

Dopunska literatura

Polymeropoulos MH, Poush J, Rubenstein JR, Francomano CA (maj 1995). "Localization of the gene (SYM1) for proximal symphalangism to human chromosome 17q21-q22". Genomics. 27 (2): 225–9. doi:10.1006/geno.1995.1035. PMID 7557985.
McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP (maj 1998). "Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite". Genes & Development. 12 (10): 1438–52. doi:10.1101/gad.12.10.1438. PMC 316831. PMID 9585504.
Brunet LJ, McMahon JA, McMahon AP, Harland RM (maj 1998). "Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton". Science. 280 (5368): 1455–7. doi:10.1126/science.280.5368.1455. PMID 9603738.
Krakow D, Reinker K, Powell B, Cantor R, Priore MA, Garber A, Lachman RS, Rimoin DL, Cohn DH (juli 1998). "Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21-22". American Journal of Human Genetics. 63 (1): 120–4. doi:10.1086/301921. PMC 1377242. PMID 9634519.
Smith WC (januar 1999). "TGF beta inhibitors. New and unexpected requirements in vertebrate development". Trends in Genetics. 15 (1): 3–5. doi:10.1016/S0168-9525(98)01641-2. PMID 10087923.
Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, Babul-Hirji R, Hudgins L, Cremers CW, Cremers FP, Brunner HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML (mart 1999). "Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis". Nature Genetics. 21 (3): 302–4. doi:10.1038/6821. PMID 10080184. S2CID 652235.
Li W, LoTurco JJ (2000). "Noggin is a negative regulator of neuronal differentiation in developing neocortex". Developmental Neuroscience. 22 (1–2): 68–73. doi:10.1159/000017428. PMID 10657699. S2CID 35547875.
Dixon ME, Armstrong P, Stevens DB, Bamshad M (2002). "Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism". Genetics in Medicine. 3 (5): 349–53. doi:10.1097/00125817-200109000-00004. PMID 11545688.
Marcelino J, Sciortino CM, Romero MF, Ulatowski LM, Ballock RT, Economides AN, Eimon PM, Harland RM, Warman ML (septembar 2001). "Human disease-causing NOG missense mutations: effects on noggin secretion, dimer formation, and bone morphogenetic protein binding". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11353–8. doi:10.1073/pnas.201367598. PMC 58733. PMID 11562478.
Paine-Saunders S, Viviano BL, Economides AN, Saunders S (januar 2002). "Heparan sulfate proteoglycans retain Noggin at the cell surface: a potential mechanism for shaping bone morphogenetic protein gradients". The Journal of Biological Chemistry. 277 (3): 2089–96. doi:10.1074/jbc.M109151200. PMID 11706034.
Takahashi T, Takahashi I, Komatsu M, Sawaishi Y, Higashi K, Nishimura G, Saito H, Takada G (decembar 2001). "Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome". Clinical Genetics. 60 (6): 447–51. doi:10.1034/j.1399-0004.2001.600607.x. PMID 11846737. S2CID 29452724.
Mangino M, Flex E, Digilio MC, Giannotti A, Dallapiccola B (mart 2002). "Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism". Human Mutation. 19 (3): 308. doi:10.1002/humu.9016. PMID 11857750. S2CID 22940188.
Brown DJ, Kim TB, Petty EM, Downs CA, Martin DM, Strouse PJ, Moroi SE, Milunsky JM, Lesperance MM (septembar 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". American Journal of Human Genetics. 71 (3): 618–24. doi:10.1086/342067. PMC 379196. PMID 12089654.
Hall AK, Burke RM, Anand M, Dinsio KJ (juli 2002). "Activin and bone morphogenetic proteins are present in perinatal sensory neuron target tissues that induce neuropeptides". Journal of Neurobiology. 52 (1): 52–60. doi:10.1002/neu.10068. PMID 12115893.
Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Izpisua Belmonte JC, Choe S (decembar 2002). "Structural basis of BMP signalling inhibition by the cystine knot protein Noggin". Nature. 420 (6916): 636–42. doi:10.1038/nature01245. PMID 12478285. S2CID 4386654.
Brown DJ, Kim TB, Petty EM, Downs CA, Martin DM, Strouse PJ, Moroi SE, Gebarski SS, Lesperance MM (mart 2003). "Characterization of a stapes ankylosis family with a NOG mutation". Otology & Neurotology. 24 (2): 210–5. doi:10.1097/00129492-200303000-00014. PMID 12621334. S2CID 26445733.

Vanjski linkovi

BMPedia - the Bone Morphogenetic Protein Wiki^{[trajno mrtav link]}
Noggin publications, gene expression data, sequences and interactants from Xenbase
NOG lokacija ljudskog genoma UCSC Genome Browser.

NOG detalji ljudskog genoma u UCSC Genome Browser.

Šablon:Superporodica receptora TGFβ modulatora

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000183691 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000048616 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: NOG noggin".

[6] Blázquez-Medela AM, Jumabay M, Boström KI (maj 2019). "Beyond the bone: Bone morphogenetic protein signaling in adipose tissue". Obesity Reviews. 20 (5): 648–658. doi:10.1111/obr.12822. PMC 6447448. PMID 30609449.

[7] Oppenheimer SB (1995). "The Discovery of Noggin". The American Biology Teacher. 57 (5): 264–266. doi:10.2307/4449989. hdl:10211.2/1126. JSTOR 4449989.

[UniProt-8] "UniProt, Q13253". Pristupljeno 24. 6. 2021.

[Hirsinger_1997-9] Hirsinger E, Duprez D, Jouve C, Malapert P, Cooke J, Pourquié O (novembar 1997). "Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning". Development. 124 (22): 4605–14. PMID 9409677.

[Marcelino_2001-10] ^ ^a ^b ^c ^d ^e ^f Marcelino J, Sciortino CM, Romero MF, Ulatowski LM, Ballock RT, Economides AN, Eimon PM, Harland RM, Warman ML (septembar 2001). "Human disease-causing NOG missense mutations: effects on noggin secretion, dimer formation, and bone morphogenetic protein binding". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11353–8. doi:10.1073/pnas.201367598. PMC 58733. PMID 11562478.

[11] Xu H, Huang W, Wang Y, Sun W, Tang J, Li D, Xu P, Guo L, Yin ZQ, Fan X (januar 2013). "The function of BMP4 during neurogenesis in the adult hippocampus in Alzheimer's disease". Ageing Research Reviews. 12 (1): 157–64. doi:10.1016/j.arr.2012.05.002. PMID 22698853. S2CID 46528212.

[12] Potti TA, Petty EM, Lesperance MM (august 2011). "A comprehensive review of reported heritable noggin-associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG-related-symphalangism spectrum disorder (NOG-SSD)" (PDF). Human Mutation. 32 (8): 877–86. doi:10.1002/humu.21515. PMID 21538686. S2CID 205920339.

[13] Liu A, Niswander LA (decembar 2005). "Bone morphogenetic protein signalling and vertebrate nervous system development". Nature Reviews. Neuroscience. 6 (12): 945–54. doi:10.1038/nrn1805. PMID 16340955. S2CID 1005572.

[14] Sawant A, Chanda D, Isayeva T, Tsuladze G, Garvey WT, Ponnazhagan S (april 2012). "Noggin is novel inducer of mesenchymal stem cell adipogenesis: implications for bone health and obesity". The Journal of Biological Chemistry. 287 (15): 12241–9. doi:10.1074/jbc.m111.293613. PMC 3320975. PMID 22351751.

[:0-15] Blázquez-Medela AM, Jumabay M, Rajbhandari P, Sallam T, Guo Y, Yao J, Vergnes L, Reue K, Zhang L, Yao Y, Fogelman AM, Tontonoz P, Lusis AJ, Wu X, Boström KI (april 2019). "Noggin depletion in adipocytes promotes obesity in mice". Molecular Metabolism. 25: 50–63. doi:10.1016/j.molmet.2019.04.004. PMC 6600080. PMID 31027994.

[16] Bok J, Brunet LJ, Howard O, Burton Q, Wu DK (novembar 2007). "Role of hindbrain in inner ear morphogenesis: analysis of Noggin knockout mice". Developmental Biology. 311 (1): 69–78. doi:10.1016/j.ydbio.2007.08.013. PMC 2215324. PMID 17900554.

[pmid21256973-17] Krause C, Guzman A, Knaus P (april 2011). "Noggin". The International Journal of Biochemistry & Cell Biology. 43 (4): 478–81. doi:10.1016/j.biocel.2011.01.007. PMID 21256973.

[Masuda-18] Masuda S, Namba K, Mutai H, Usui S, Miyanaga Y, Kaneko H, Matsunaga T (maj 2014). "A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss". Biochemical and Biophysical Research Communications. 447 (3): 496–502. doi:10.1016/j.bbrc.2014.04.015. PMID 24735539.

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