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Bellesso, Stefania (2017) Deregulated FGF signaling substantially contributes to early osteogenic defects in Mucopolysaccharidosis type II. [Tesi di dottorato]

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Abstract (inglese)

FGF signaling is a key pathway strictly involved in many stages of ossification and gain of function mutations of many FGF pathway components have been associated with bone diseases like craniosynostosis and chondrodysplasia. The fine-tuning of the FGF signaling pathway is achieved at different levels, both intracellularly and by extracellular glycosaminoglycans (GAGs), which play a critical role in ligand and receptor binding. In this work, I show that the deficiency of iduronate 2-sulfatase (IDS), which is involved in GAGs catabolism, perturbs FGF signaling leading to early bone defects before the onset of evident massive GAGs storage.
A defective IDS activity causes a rare lysosomal storage disease called Mucopolysaccharidosis type II, in which skeletal abnormalities represent one of the major disabling aspects. Enzyme replacement therapy (ERT) is the currently available therapeutic option, which, however, suffer from limited efficacy.
To better elucidate early alterations of bone development occurring in MPSII, I took advantage of the zebrafish model, given its easy genetic manipulation and the evolutionary conserved mechanisms and signaling pathways regulating bone formation. In particular, I generated zebrafish models for MPSII, using a morpholino-based knock down technology and CRISPR/Cas9 technique, respectively. Using different approaches, including in situ hybridization and transgenesis, I demonstrated that the altered IDS function affects the expression of key FGF signaling markers and bone differentiation markers at early life stages, before any massive glycosaminoglycans accumulation is detectable.
The involvement of the FGF signaling downstream to the IDS loss of function was also detected in cranial and appendicular bones of IDS knockout mice and in Hunter patient fibroblasts. Therefore, the results of this study suggest that in MPSII an early FGF signaling impairment, due to IDS deficit, may cause a dysregulated expression of genes involved in bone development before the occurrence of lysosomal GAGs accumulation.

Abstract (italiano)

La via di segnale FGF è una importante pathway coinvolta in diverse fasi dell’osteogenesi e mutazioni che colpiscono componenti di questa via sono associate a diverse malattie umane come le craniosinostosi e le condrodisplasie. La regolazione della via di segnale FGF avviene a diversi livelli, sia con meccanismi intracellulari che tramite l’interazione con i glicosaminoglicani (GAGs) presenti nella matrice extracellulare, i quali possiedono un ruolo critico nell’interazione fra ligando e recettore.
In questo lavoro viene dimostrato che alterazioni nella funzionalità dell’enzima iduronato 2-sulfatasi (IDS), coinvolto nel catabolismo dei GAGs, sono responsabili dell’alterazione della via di segnale FGF.
La mancata o deficitaria attività dell’enzima IDS è causa dell’insorgenza di una rara patologia da accumulo lisosomiale chiamata Mucopolisaccaridosi di tipo II, nella quale uno degli aspetti più disabilitanti è rappresentato da manifestazioni patologiche dell’apparato scheletrico. La terapia comunemente impiegata è la somministrazione dell’enzima ricombinante (Enzyme Replacement Therapy, ERT) che, pur determinando un miglioramento di una parte della sintomatologia, non risulta efficace, o comunque risulta scarsamente efficace, in distretti importanti come cuore e sistema scheletrico.
Per lo studio della patogenesi molecolare della MPSII e la comprensione dei meccanismi patogenetici che inducono alterazioni precoci nello sviluppo osseo, è stato utilizzato lo zebrafish come modello. Zebrafish risulta infatti un buon modello perché semplice da manipolare geneticamente; inoltre, in esso, il controllo delle principali vie di segnale che regolano il suo sviluppo osseo è altamente conservato.
Sono stati generati sia modelli transienti con l’utilizzo della tecnica oligo morfolino, sia un mutante stabile applicando il metodo Crispr/Cas9. Utilizzando diversi approcci sperimentali, comprese tecniche di ibridazione in situ e transgenesi, è stato dimostrato che la mancata funzionalità dell’IDS determina alterazioni nell’espressione di marcatori chiave della via di segnale FGF e della differenziazione ossea a stadi molto precoci, prima di un evidente accumulo di glicosaminoglicani nei tessuti.
L’alterazione di questa pathway è stata osservata anche in campioni di ossa craniche e appendicolari di topi IDS-KO e in fibroblasti di pazienti Hunter.
I risultati di questo studio suggeriscono dunque che nella MPSII disfunzioni dell’enzima IDS inducano, in fasi precoci, alterazioni nella regolazione della via di segnale FGF, che a loro volta possono essere responsabili dell’alterata espressione di geni coinvolti nello sviluppo osseo, prima che si verifichi l’accumulo dei GAGs nei lisosomi.

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Tipo di EPrint:Tesi di dottorato
Relatore:Scarpa, Maurizio
Dottorato (corsi e scuole):Ciclo 29 > Corsi 29 > MEDICINA DELLO SVILUPPO E SCIENZE DELLA PROGRAMMAZIONE SANITARIA
Data di deposito della tesi:30 Gennaio 2017
Anno di Pubblicazione:30 Gennaio 2017
Parole chiave (italiano / inglese):Zebrafish, Mucopolysaccharidosis type II, Iduronate 2-sulfatase, Iduronato 2 solfatasi, Mucopolisaccaridosi di tipo II
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/13 Biologia applicata
Struttura di riferimento:Dipartimenti > Dipartimento di Salute della Donna e del Bambino
Codice ID:10081
Depositato il:09 Nov 2017 12:17
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Aldenhoven M, Sakkers RJB, Boelens J, De Koning TJ, Wulffraat NM. Musculoskeletal manifestations of lysosomal storage disorders. Ann Rheum Dis 2009; 68:1659-1665 Cerca con Google

Al Sawaf S, Mayatepek E, Hoffmann B. Neurological findings in Hunter disease: Pathology and possible therapeutic effects reviewed. J Inherit Metab Dis. 2008 Aug;31(4):473-80. Cerca con Google

Appelqvist H, Wäster P, Kågedal K, Öllinger K. The lysosome : from waste bag to potential therapeutic target. J Mol Cell Biol. 2013 Aug; 5(4):214-26. Cerca con Google

Arya M, Shergill IS, Williamson M, Gommersall L, Arya N, Patel HRH. Basic principles of real-time quantitative PCR. Expert Rev.Mol. Diagn. 2005; 5(2):209-219. Cerca con Google

Aszodi A, Bateman JF, Gustafsson E, Boot-Handford R, Fassler R. Mammalian skeletogenesis and extracellular matrix : What can we learn from knockout mice? Cell Struct Funct. 2000; 25:73–84. Cerca con Google

Baek WY, Lee MA, Jung JW, Kim SY, Akiyama H, de Crombrugghe B, Kim JE. Positive regulation of adult bone formation by osteoblast-specific transcription factor osterix. J Bone Miner Res. 2009 Jun;24(6):1055-65. Cerca con Google

Ballabio A, Gieselmann V. Lysosomal disorders : From storage to cellular damage. Biochim Biophys Acta. 2009 Apr;1793(4):684-96 Cerca con Google

Balzano N, Villani GR, Grosso M, Izzo P, Di Natale P. Detection of four novel mutations in the iduronate-2-sulfatase gene. Hum Mutat. 1998;11(4):333. Cerca con Google

Behonick DJ, Werb Z. A bit of give and take : the relationship between the extracellular matrix and the developing chondrocyte. Mech Dev. 2003 Nov;120(11):1327-36. Cerca con Google

Berkovits BD, Mayr C. Alternative 3' UTRs act as scaffolds to regulate membrane protein localization. Nature. 2015 Jun 18;522(7556):363-7. Cerca con Google

Bonuccelli G, Regis S, Filocamo M, Corsolini F, Caroli F, Gatti R. A deletion involving exons 2-4 in the iduronate-2-sulfatase gene of a patient with intermediate Hunter syndrome. Clin Genet. 1998 Jun;53(6):474-7. Cerca con Google

Bonuccelli G, Di Natale P, Corsolini F, Villani G, Regis S, Filocamo M. The effect of four mutations on the expression of iduronate-2-sulfatase in mucopolysaccharidosis type II. Biochim Biophys Acta. 2001 Nov 29;1537(3):233-8. Cerca con Google

Boustany RN. Lysosomal storage diseases -- the horizon expands. Nat Rev Neurol. 2013 Oct;9(10):583-98. Cerca con Google

Casari A, Schiavone M, Facchinello N, Vettori A, Meyer D, Tiso N, Moro E, Argenton F. A Smad3 transgenic reporter reveals TGF-beta control of zebrafish spinal cord development. Dev Biol. 2014 Dec 1;396(1):81-93. Cerca con Google

Chen P, Cescon M, Zuccolotto G, Nobbio L, Colombelli C, Filaferro M, Vitale G, Feltri ML, Bonaldo P. Collagen VI regulates peripheral nerve regeneration by modulating macrophage recruitment and polarization. Acta Neuropathol. 2015 Jan;129(1):97-113. Cerca con Google

Chkioua L, Khedhiri S, Ferchichi S, Tcheng R, Chahed H, Froissart R, Vianey-Saban C, Laradi S, Miled A. Molecular analysis of iduronate -2- sulfatase gene in Tunisian patients with mucopolysaccharidosis type II. Diagn Pathol. 2011 May 23;6:42. Cerca con Google

Chistiakov DA, Kuzenkova LM, Savost'anov KV, Gevorkyan AK, Pushkov AA, Nikitin AG, Vashakmadze ND, Zhurkova NV, Podkletnova TV, Namazova-Baranova LS, Baranov AA. Genetic Analysis of 17 Children with Hunter Syndrome: Identification and Functional Characterization of Four Novel Mutations in the Iduronate-2-Sulfatase Gene. J Genet Genomics. 2014 Apr 20;41(4):197-203. Cerca con Google

Clarke LA. Pathogenesis of skeletal and connective tissue involvement in the mucopolysaccharidoses : glycosaminoglycan storage is merely the instigator. Rheumatology (Oxford). 2011 Dec;50 Suppl 5:v13-8. Cerca con Google

Clarke LA, Hollak CE. The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders. Best Pract Res Clin Endocrinol Metab. 2015 Mar;29(2):219-35. Cerca con Google

Corallo D, Schiavinato A, Trapani V, Moro E, Argenton F, Bonaldo P. Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals. Development. 2013 Nov;140(22):4594-601 Cerca con Google

Deckelbaum RA, Majithia A, Booker T, Henderson JE, Loomis CA. The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling. Development. 2006 Jan;133(1):63-74. Cerca con Google

Dravis C, Spike BT, Harrell JC, Johns C, Trejo CL, Southard-Smith EM, Perou CM, Wahl GM. Sox10 Regulates Stem / Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells. Cell Rep. 2015 Sep 29;12(12):2035-48. Cerca con Google

Felber K, Elks PM, Lecca M, Roehl HH. Expression of osterix Is Regulated by FGF and Wnt / β -Catenin Signalling during Osteoblast Differentiation. PLoS One. 2015 Dec 21;10(12):e0144982. Cerca con Google

Flanagan-Steet H, Sias C, Steet R. Altered chondrocyte differentiation and extracellular matrix homeostasis in a zebrafish model for mucolipidosis II. Am J Pathol. 2009 Nov;175(5):2063-75. Cerca con Google

Garcia AR, Pan J, Lamsa JC, Muenzer J. The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome). J Inherit Metab Dis. 2007 Nov;30(6):924-34. Cerca con Google

Giugliani R, Federhen A, Rojas MV, Vieira T, Artigalás O, Pinto LL, Azevedo AC, Acosta A, Bonfim C, Lourenço CM, Kim CA, Horovitz D, Bonfim D, Norato D, Marinho D, Palhares D, Santos ES, Ribeiro E, Valadares E, Guarany F, de Lucca GR, Pimentel H, de Souza IN, Correa J Sr, Fraga JC, Goes JE, Cabral JM, Simionato J, Llerena J Jr, Jardim L, Giuliani L, da Silva LC, Santos ML, Moreira MA, Kerstenetzky M, Ribeiro M, Ruas N, Barrios P, Aranda P, Honjo R, Boy R, Costa R, Souza C, Alcantara FF, Avilla SG, Fagondes S, Martins AM. Mucopolysaccharidosis I , II , and VI : Brief review and guidelines for treatment. Genet Mol Biol. 2010 Oct;33(4):589-604. Cerca con Google

Gökdoğan Ç, Altinyay Ş, Gökdoğan O, Tutar H, Gündüz B, Okur İ, Tümer L, Kemaloğlu YK. Audiologic evaluations of children with mucopolysaccharidosis. Braz J Otorhinolaryngol. 2016 May-Jun;82(3):281-4. Cerca con Google

Hammond CL, Schulte-merker S. Two populations of endochondral osteoblasts with differential sensitivity to Hedgehog signalling. Development. 2009 Dec; 136(23):3991-4000. Cerca con Google

Hammond CL, Moro E. Using transgenic reporters to visualize bone and cartilage signaling during development in vivo. Front Endocrinol (Lausanne). 2012 Jul 18;3:91. Cerca con Google

Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003 May 15;423(6937):349-55. Cerca con Google

Heppner JM, Zaucke F, Clarke LA. Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I. Mol Genet Metab. 2015 Feb;114(2):146-55. Cerca con Google

Inoue D, Wittbrodt J. One for All — A Highly Efficient and Versatile Method for Fluorescent Immunostaining in Fish Embryos. PLoS One. 2011;6(5):e19713. Cerca con Google

Isogai K, Sukegawa K, Tomatsu S, Fukao T, Song XQ, Yamada Y, Fukuda S, Orii T, Kondo N. Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with mucopolysaccharidosis type II ( Hunter disease ). J Inherit Metab Dis. 1998 Feb;21(1):60-70. Cerca con Google

Jao L, Wente SR, Chen W. Efficient multiplex biallelic zebra fi sh genome editing using a CRISPR nuclease system. Proc Natl Acad Sci U S A. 2013 Aug 20 ; 110(34): 13904-9. Cerca con Google

Kague E, Gallagher M, Burke S, Parsons M, Franz-Odendaal T, Fisher S. Skeletogenic Fate of Zebrafish Cranial and Trunk Neural Crest. PLoS One. 2012;7(11):e47394. Cerca con Google

Kato T, Kato Z, Kuratsubo I, Tanaka N, Ishigami T, Kajihara J, Sukegawa-Hayasaka K, Orii K, Isogai K, Fukao T, Shimozawa N, Orii T, Kondo N, Suzuki Y. Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II. J Hum Genet. 2005;50(8):395-402. Cerca con Google

Kawakami M, Yamamura K. Cranial bone morphometric study among mouse strains. BMC Evol Biol. 2008 Feb 29;8:73 Cerca con Google

Kingma SD, Wagemans T, IJlst L, Bronckers AL, van Kuppevelt TH, Everts V, Wijburg FA, van Vlies N.Altered interaction and distribution of glycosaminoglycans and growth factors in mucopolysaccharidosis type I bone disease. Bone. 2016 Jul;88:92-100. Cerca con Google

Kirby BB, Takada N, Latimer AJ, Shin J, Carney TJ, Kelsh RN, Appel B. In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development. Nat Neurosci. 2006 Dec;9(12):1506-11. Cerca con Google

Korzh S, Pan X, Garcia-Lecea M, Winata CL, Pan X, Wohland T, Korzh V, Gong Z. Requirement of vasculogenesis and blood circulation in late stages of liver growth in zebrafish. BMC Dev Biol. 2008 Sep 16;8:84. Cerca con Google

Lieschke GJ, Currie PD. Animal models of human disease : zebrafish swim into view. Nat Rev Genet. 2007 May;8(5):353-67. Cerca con Google

Lin SM, Lin HY, Chuang CK, Lin SP, Chen MR. Cardiovascular abnormalities in Taiwanese patients with mucopolysaccharidosis. Mol Genet Metab. 2014 Apr;111(4):493-8. Cerca con Google

Lu P, Takai K, Weaver VM, Werb Z. Extracellular Matrix Degradation and Remodeling in Development and Disease. Cold Spring Harb Perspect Biol. 2011 Dec 1;3(12). Cerca con Google

Lualdi S, Di Rocco M, Corsolini F, Spada M, Bembi B, Cotugno G, Battini R, Stroppiano M, Gabriela Pittis M, Filocamo M. Identification of nine new IDS alleles in mucopolysaccharidosis II . Quantitative evaluation by real-time RT-PCR of mRNAs sensitive to nonsense-mediated and nonstop decay mechanisms. Biochim Biophys Acta. 2006 Apr;1762(4):478-84. Cerca con Google

Lualdi S, Tappino B, Di Duca M, Dardis A, Anderson CJ, Biassoni R, Thompson PW, Corsolini F, Di Rocco M, Bembi B, Regis S, Cooper DN, Filocamo M. Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome. Hum Mutat. 2010 Apr;31(4):E1261-85. Cerca con Google

Mackay EW, Apschner A, Schulte-Merker S. A bone to pick with zebrafish. Bonekey Rep. 2013 Nov 13;2:445. Cerca con Google

Mandal C, Baek MN, Jung KH, Chai JC, Lee YS, Chai YG. Gene expression profile associated with the reversine-mediated transdifferentiation of NIH-3T3 fibroblast cells into osteoblasts. BioChip Journal, 7(3), 278–287. Cerca con Google

Martin R, Beck M, Eng C, Giugliani R, Harmatz P, Muñoz Vand Muenzer J. Recognition and diagnosis of mucopolysaccharidosis II (Hunter Syndrome). Pediatrics. 2008; 121:377-386. Cerca con Google

McKeehan WL, Wang F, Luo Y. The fibroblast growth factor (FGF) signaling complex. Handbook of Cell Signaling, 2nd ed; Volume I, Chapter 38. New York: Academic/Elsevier Press; 2009. pp. 253–259. Cerca con Google

Mitchell RE, Huitema LF, Skinner RE, Brunt LH, Severn C, Schulte-Merker S, Hammond CL. New tools for studying osteoarthritis genetics in zebrafish. Osteoarthritis Cartilage. 2013 Feb;21(2):269-78. Cerca con Google

Molina G,Vogt A, Bakan A,Dai W, Queiroz de Oliveira P, Znosko W, Smithgall TE, Bahar I, Lazo JS, Day BW, Tsang M. Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat Chem Biol. 2009 Sep; 5(9): 680–687. Cerca con Google

Moreira da Silva I, Froissart R, Marques dos Santos H, Caseiro C, Maire I, Bozon D. Molecular basis of Mucopolysaccharidosis type II in Portugal : identification of four novel mutations. Clin Genet. 2001 Oct;60(4):316-8. Cerca con Google

Morini SR, Steiner CE, Gerson LB. Mucopolysaccharidosis type II : skeletal – muscle system involvement. J Pediatr Orthop B. 2010 Jul;19(4):313-7. Cerca con Google

Moro E, Tomanin R, Friso A, Modena N, Tiso N, Scarpa M, Argenton F. A novel functional role of iduronate-2-sulfatase in zebrafish early development. Matrix Biology 2010; 29(1), 43–50. Cerca con Google

Moro E, Ozhan-Kizil G, Mongera A, Beis D, Wierzbicki C, Young RM, Bournele D, Domenichini A, Valdivia LE, Lum L, Chen C, Amatruda JF, Tiso N, Weidinger G, Argenton F. In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains. Dev Biol. 2012 Jun 15;366(2):327-40. Cerca con Google

Moro E, Vettori A, Porazzi P, Schiavone M, Rampazzo E, Casari A, Ek O, Facchinello N, Astone M, Zancan I, Milanetto M, Tiso N, Argenton F. Generation and application of signaling pathway reporter lines in zebrafish. Mol Genet Genomics. 2013 Jun;288(5-6):231-42. Cerca con Google

Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004 May;144(5 Suppl):S27-34. Cerca con Google

Opoka-Winiarska V, Jurecka A, Emeryk A, Tylki-Szymańska A. Osteoimmunology in mucopolysaccharidoses type I , II , VI and VII . Immunological regulation of the osteoarticular system in the course of metabolic inflammation. Osteoarthritis Cartilage. 2013 Dec;21(12):1813-23. Cerca con Google

Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 2002 Jun 15;16(12): 1446-65. Cerca con Google

Ornitz DM, Marie PJ. Fibroblast growth factor signaling in skeletal development and disease. Genes Dev. 2015 Jul 15;29(14):1463-86. Cerca con Google

Patel P, Suzuki Y, Maeda M, Yasuda E, Shimada T, Orii KE, Orii T, Tomatsu S. Growth charts for patients with Hunter syndrome. Mol Genet Metab Rep. 2014;1:5-18. Cerca con Google

Petrey AC, Flanagan-Steet H, Johnson S, Fan X, De la Rosa M, Haskins ME, Nairn AV, Moremen KW, Steet R. Excessive activity of cathepsin K is associated with cartilage defects in a zebrafish model of mucolipidosis II. Dis Model Mech. 2012 Mar;5(2):177-90. Cerca con Google

Polgreen LE, Thomas W, Fung E, Viskochil D, Stevenson DA, Steinberger J, Orchard P, Whitley CB, Ensrud KE. Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI. J Clin Densitom. 2014 Jan-Mar;17(1):200-6. Cerca con Google

Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res. 2005 Feb;8(1):11-7. Cerca con Google

Schilling TF. Genetic analysis of craniofacial development in the vertebrate embryo. Bioessays. 1997 Jun;19(6):459-68. Cerca con Google

Settembre C, Fraldi A, Medina DL, Ballabio A. Signals from the lysosome : a control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol. 2013 May;14(5):283-96. Cerca con Google

Simonaro CM, D'Angelo M, Haskins ME, Schuchman EH.. Joint and Bone Disease in Mucopolysaccharidoses VI and VII : Identification of New Therapeutic Targets and BioMarkers Using Animal Models. Pediatr Res. 2005 May;57(5 Pt 1):701-7. Cerca con Google

Spoorendonk KM, Peterson-Maduro J, Renn J, Trowe T, Kranenbarg S, Winkler C, Schulte-Merker S. Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. Development. 2008 Nov;135(22):3765-74. Cerca con Google

Su N, Jin M, Chen L. Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. Bone Res. 2014 Apr 29;2:14003. Cerca con Google

Sukegawa-Hayasaka K, Kato Z, Nakamura H, Tomatsu S, Fukao T, Kuwata K, Orii T, Kondo N. Effect of Hunter disease ( mucopolysaccharidosis type II ) mutations on molecular phenotypes of iduronate-2-sulfatase : Enzymatic activity , protein processing and structural analysis. J Inherit Metab Dis. 2006 Dec;29(6):755-61. Cerca con Google

Suzuki T, Sakai D, Osumi N, Wada H, Wakamatsu Y. Sox genes regulate type 2 collagen expression in avian neural crest cells. Dev Growth Differ. 2006 Oct;48(8):477-86. Cerca con Google

Teven CM, Farina EM, Rivas J, Reid RR. Fibroblast growth factor (FGF) signaling in development and skeletal diseases. Genes Dis. 2014 Dec 1;1(2):199-213. Cerca con Google

Tomatsu S, Alméciga-Díaz CJ, Montaño AM, Yabe H, Tanaka A, Dung VC, Giugliani R, Kubaski F, Mason RW, Yasuda E, Sawamoto K, Mackenzie W, Suzuki Y, Orii KE, Barrera LA, Sly WS, Orii T. Therapies for the bone in mucopolysaccharidoses. Mol Genet Metab. 2015 Feb;114(2):94-109 Cerca con Google

Tsang KY, Cheung MC, Chan D, Cheah KS. The developmental roles of the extracellular matrix : beyond structure to regulation. Cell Tissue Res. 2010 Jan;339(1):93-110. Cerca con Google

Tumova S, Woods A, Couchman JR. Heparan sulfate proteoglycans on the cell surface : versatile coordinators of cellular functions. Int J Biochem Cell Biol. 2000 Mar;32(3):269-88. Cerca con Google

Vafiadaki E, Cooper A, Heptinstall LE, Hatton CE, Thornley M, Wraith JE. Mutation analysis in 57 unrelated patients with MPS II (Hunter ’ s disease). Arch Dis Child. 1998 Sep;79(3):237-41. Cerca con Google

Wraith JE. Lysosomal disorders. Paediatrics and Child Health. 2011 Feb; 21(2:) 76–79. Cerca con Google

Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Cerca con Google

Znosko WA, Yu S, Thomas K, Molina GA, Li C, Tsang W, Dawid IB, Moon AM, Tsang M. Overlapping functions of Pea3 ETS transcription factors in FGF signaling during zebra fi sh development. Dev Biol. 2010 Jun 1;342(1):11-25. Cerca con Google

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