Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2 +P253R mice
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- 作者：Yingli Wang (1)
Miao Sun (2) (3)
Victoria L Uhlhorn (1)
Xueyan Zhou (1)
Inga Peter (1)
Neus Martinez-Abadias (4)
Cheryl A Hill (4)
Christopher J Percival (4)
Joan T Richtsmeier (4) (5)
David L Huso (6)
Ethylin Wang Jabs (1) (2) - 刊名：BMC Developmental Biology
- 出版年：2010
- 出版时间：December 2010
- 年：2010
- 卷：10
- 期：1
- 全文大小：10763KB
- 参考文献：1. Johnson DE, Lee PL, Lu J, Williams LT: Diverse forms of a receptor for acidic and basic fibroblast growth factors. / Mol Cell Biol 1990, 10:4728-736.
2. Olsen SK, Ibrahimi OA, Raucci A, Zhang F, Eliseenkova AV, Yayon A, Basilico C, Linhardt RJ, Schlessinger J, Mohammadi M: Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity. / Proc Natl Acad Sci USA 2004, 101:935-40. CrossRef
3. Eswarakumar VP, Lax I, Schlessinger J: Cellular signaling by fibroblast growth factor receptors. / Cytokine Growth Factor Rev 2005, 16:139-49. CrossRef
4. Ornitz DM, Itoh N: Fibroblast growth factors. / Genome Biol 2001, 2:reviews3005. CrossRef
5. Miki T, Bottaro DP, Fleming TP, Smith CL, Burgess WH, Chan AM, Aaronson SA: Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. / Proc Natl Acad Sci USA 1992, 89:246-50. CrossRef
6. Orr-Urtreger A, Bedford MT, Burakova T, Arman E, Zimmer Y, Yayon A, Givol D, Lonai P: Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). / Dev Biol 1993, 158:475-86. CrossRef
7. Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M: Receptor specificity of the fibroblast growth factor family. / J Biol Chem 1996, 271:15292-5297. CrossRef
8. Schlessinger J: Cell signaling by ceceptor tyrosine kinases. / Cell 2000, 103:211-25. CrossRef
9. Dailey L, Ambrosetti D, Mansukhani A, Basilico C: Mechanisms underlying differential responses to FGF signaling. / Cytokine Growth Factor Rev 2005, 16:233-47. CrossRef
10. Hu Y, Chan E, Wang SX, Li B: Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation. / Endocrinology 2003, 144:2068-074. CrossRef
11. Wang X, Goh CH, Li B: p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix. / Endocrinology 2007, 148:1629-637. CrossRef
12. Xiao G, Jiang D, Gopalakrishnan R, Franceschi RT: Fibroblast growth factor 2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the osteoblast transcription factor, Cbfa1/Runx2. / J Biol Chem 2002, 277:36181-6187. CrossRef
13. Raucci A, Bellosta P, Grassi R, Basilico C, Mansukhani A: Osteoblast proliferation or differentiation is regulated by relative strengths of opposing signaling pathways. / J Cell Physio 2008, 215:442-51. CrossRef
14. Marie PJ: Fibroblast growth factor signaling controlling osteoblast differentiation. / Gene 2003, 316:23-2. CrossRef
15. Debiais F, Lemonnier J, Hay E, Delannoy P, Caverzasio J, Marie PJ: Fibroblast growth factor-2(FGF-2) increases N-cadherin expression through protein kinase C and Src-kinase pathways in human calvaria osteoblasts. / J Cell Biochem 2001, 81:68-1. CrossRef
16. Jiang X, Iseki S, Maxson RE, Sucov HM, Morriss-Kay GM: Tissue origins and interactions in the mammalian skull vault. / Dev Biol 2002, 241:106-16. CrossRef
17. Iseki S, Wilkie AO, Heath JK, Ishimaru T, Eto K, Morriss-Kay GM: Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2. / Development 1997, 124:3375-384.
18. Rice DP, Aberg T, Chan Y, Tang Z, Kettunen PJ, Pakarinen L, Maxson RE, Thesleff I: Integration of FGF and TWIST in calvarial bone and suture development. / Development 2000, 127:1845-855.
19. Olsen BR, Reginato AM, Wang W: Bone development. / Annu Rev Cell Dev Biol 2000, 16:191-20. CrossRef
20. McBratney-Owen B, Iseki S, Bamforth SD, Olsen BR, Morriss-Kay GM: Development and tissue origins of the mammalian cranial base. / Dev Biol 2008, 322:121-32. CrossRef
21. Gross JB, Hanken J: Review of fate-mapping studies of osteogenic cranial neural crest in vertebrates. / Dev Biol 2008,15:317(2):389-00. CrossRef
22. Iseki S, Wilkie AO, Morriss-Kay GM: Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. / Development 1999, 126:5611-620.
23. Ohbayashi N, Shibayama M, Kurotaki Y, Imanishi M, Fujimori T, Itoh N, Takada S: FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. / Genes Dev 2002, 16:870-79. CrossRef
24. Cohen MM Jr, Kreiborg S: Suture formation, premature sutural fusion, and suture default zones in Apert syndrome. / Am J Med Genet 1996, 62:339-44. Publisher Full Text CrossRef
25. Wilkie AO, Slaney SF, Oldridge M, Poole MD, Ashworth GJ, Hockley AD, Hayward RD, David DJ, Pulleyn LJ, Rutland P: Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. / Nat Genet 1995, 9:165-72. CrossRef
26. Park WJ, Theda C, Maestri NE, Meyers GA, Fryburg JS, Dufresne C, Cohen MM Jr, Jabs EW: Analysis of phenotypic features and FGFR2 mutations in Apert syndrome. / Am J Hum Genet 1995, 57:321-28.
27. Anderson J, Burns HD, Enriquez-Harris P, Wilkie AO, Heath JK: Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand. / Hum Mol Genet 1998, 7:1475-483. CrossRef
28. Yu K, Herr AB, Waksman G, Ornitz DM: Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome. / Proc Natl Acad Sci USA 2000, 97:14536-4541. CrossRef
29. Ibrahimi OA, Eliseenkova AV, Plotnikov AN, Yu K, Ornitz DM, Mohammadi M: Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome. / Proc Natl Acad Sci USA 2001, 98:7182-187. CrossRef
30. Lomri A, Lemonnier J, Hott M, Parseval Nde, Lajeunie E, Munnich A, Renier D, Marie PJ: Increased calvaria cell differentiation and bone matrix formation induced by fibroblast growth factor receptor 2 mutations in Apert syndrome. / J Clin Invest 1998, 101:1310-317.
31. Fragale A, Tartaglia M, Bernardini S, Di Stasi AM, Di Rocco C, Velardi F, Teti A, Battaglia PA, Migliaccio S: Decreased proliferation and altered differentiation in osteoblasts from genetically and clinically distinct craniosynostotic disorders. / Am J Pathol 1999, 154:1465-477. CrossRef
32. Lemonnier J, Ha? E, Delannoy P, Fromigué O, Lomri A, Modrowski D, Marie PJ: Increased osteoblast apoptosis in Apert craniosynostosis: Role of protein kinase C and interleukin-1. / Am J Pathol 2001, 158:1833-842. CrossRef
33. Chen L, Li D, Li C, Engel A, Deng CX: A Ser250Trp substitution in mouse fibroblast growth factor receptor 2 Fgfr2 results in craniosynostosis. / Bone 2003, 33:169-78. CrossRef
34. Wang Y, Xiao R, Yang F, Karim BO, Iacovelli AJ, Cai J, Lerner CP, Richtsmeier JT, Leszl JM, Hill CA, Yu K, Ornitz DM, Elisseeff J, Huso DL, Jabs EW: Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse. / Development 2005, 132:3537-548. CrossRef
35. Yin L, Du X, Li C, Xu X, Chen Z, Su N, Zhao L, Qi H, Li F, Xue J, Yang J, Jin M, Deng C, Chen L: A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis. / Bone 2008, 42:631-3. CrossRef
36. Holmes G, Rothschild G, Roy UB, Deng CX, Mansukhani A, Basilico C: Early onset of craniosynostosis in an Apert mouse model reveals critical features of this pathology. / Dev Biol 2009, 328:273-84. CrossRef
37. Shukla V, Coumoul X, Wang RH, Kim HS, Deng CX: RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis. / Nat Genet 2007, 39:1145-150. CrossRef
38. Richtsmeier JT, Lele S: A coordinate-free approach to the analysis of growth patterns: models and theoretical considerations. / Biol Rev Camb Philos Soc 1993, 68:381-11. CrossRef
39. Apert ME: De l'acrocephalosyndactylie. / Bulletin de la Société des médecins des h?pitaux de Paris 1906, 23:1310-313.
40. Cohen MM: / Craniosynostosis: Diagnosis, Evaluation, and. Management. New York Raven Press; 1986.
41. Kreiborg S, Cohen MM Jr: The oral manifestations of Apert syndrome. / J Craniofac Genet Dev Biol 1992, 3:41-8.
42. Slaney SF, Oldridge M, Hurst JA, Moriss-Kay GM, Hall CM, Poole MD, Wilkie AO: Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome. / Am J Hum Genet 1996, 58:923-32.
43. von Gernet S, Golla A, Ehrenfels Y, Schuffenhauer S, Fairley JD: Genotype-phenotype analysis in Apert syndrome suggests opposite effects of the two recurrent mutations on syndactyly and outcome of craniofacial surgery. / Clin Genet 2000, 57:137-39. CrossRef
44. Sannomiya EK, Reis SAB, Asaumi J, Barbara AS, Kishi K: Clinical and radiographic presentation and preparation of the prototyping model for pre-surgical planning in Apert's syndrome. / Dentomaxillofac Radiol 2006, 35:119-24. CrossRef
45. Baroni T, Carinci P, Lilli C, Bellucci C, Aisa MC, Scapoli L, Volinia S, Carinci F, Pezzetti F, Calvitti M, Farina A, Conte C, Bodo M: P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation. / J Cell Physiol 2005, 202:524-35. CrossRef
46. Yang F, Wang Y, Zhang Z, Hsu B, Jabs EW, Elisseeff JH: The study of abnormal bone development in the Apert syndrome Fgfr2+/S252W mouse using a 3D hydrogel culture model. / Bone 2008, 43:55-3. CrossRef
47. Morriss-Kay GM, Wilkie AO: Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies. / J Anat 2005, 207:637-53. CrossRef
48. Hajihosseini MK: Fibroblast growth factor signaling in cranial suture development and pathogenesis. / Front Oral Biol 2008, 12:160-77. Review CrossRef
49. Carver EA, Oram KF, Gridley T: Craniosynostosis in Twist heterozygous mice: a model for Saethre-Chotzen syndrome. / Anat Rec 2002, 268:90-2. CrossRef
50. Zhou YX, Xu X, Chen L, Li C, Brodie SG, Deng CX: A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures. / Hum Mol Genet 2000, 9:2001-008. CrossRef
51. Hajihosseini MK, Wilson S, De Moerlooze L, Dickson C: A splicing switch and gain-of-function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-syndrome-like phenotypes. / Proc Natl Acad Sci 2001, 98:3855-860. CrossRef
52. Eswarakumar VP, Monsonego-Ornan E, Pines M, Antonopoulou I, Morriss-Kay GM, Lonai P: A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis. / Proc Natl Acad Sci USA 2004, 101:12555-2560. CrossRef
53. Yu HM, Jerchow B, Sheu TJ, Liu B, Costantini F, Puzas JE, Birchmeier W, Hsu W: The role of Axin2 in calvarial morphogenesis and craniosynostosis. / Development 2005, 132:1995-005. CrossRef
54. Twigg SR, Healy C, Babbs C, Sharpe JA, Wood WG, Sharpe PT, Morriss-Kay GM, Wilkie AO: Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome. / Dev Dyn 2009, 238:331-42. CrossRef
55. Merrill AE, Bochukova EG, Brugger SM, Ishii M, Pilz DT, Wall SA, Lyons KM, Wilkie AO, Maxson RE Jr: Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. / Hum Mol Genet 2006, 15:1319-328. CrossRef
56. Ting MC, Wu NL, Roybal PG, Sun J, Liu L, Yen Y, Maxson RE Jr: EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. / Development 2009, 136:855-64. CrossRef
57. Johnson D, Iseki S, Wilkie AO, Morriss-Kay GM: Exression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for twist in suture initiation and biogenesis. / Mech Dev 2000, 91:341-45. CrossRef
58. Jabs EW, Li X, Scott AF, Meyers G, Chen W, Eccles M, Mao JI, Charnas LR, Jackson CE, Jaye M: Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. / Nat Genet 1994, 8:275-79. CrossRef
59. Marie PJ, Kaabeche K, Guenou H: Roles of FGFR2 and twist in human craniosynostosis: insights from genetic mutations in cranial osteoblasts. / Front Oral Biol 2008, 12:144-59. CrossRef
60. el Ghouzzi V, Le Merrer M, Perrin-Schmitt F, Lajeunie E, Benit P, Renier D, Bourgeois P, Bolcato-Bellemin AL, Munnich A, Bonaventure J: Mutations of the TWIST gene in the Saethre-Chotzen syndrome. / Nat Genet 1994, 15:42-6. CrossRef
61. Connerney J, Andreeva V, Leshem Y, Mercado MA, Dowell K, Yang X, Lindner V, Friesel RE, Spicer DB: Twist1 homodimers enhance FGF responsiveness of the cranial sutures and promote suture closure. / Dev Biol 2008, 318:323-34. CrossRef
62. Hogan B, Beddington R, Constantini F, Lacy E: Staining embryos for cartilage and bone. In / Manipulating the Mouse Embryo: A Laboratory Manual. 2nd edition. Plainview, New York: Cold Spring Harbor Laboratory Press; 1994:379.
63. Corner BD, Lele S, Richtsmeier JT: Measuring precision of three-dimensional landmark data. / Quant Anthropol 1992, 3:347-59.
64. Richtsmeier JT, Paik C, Elfert P, Cole TI, Dahlman H: Precision, repeatability, and validation of the localization of cranial landmarks using computed tomography scans. / Cleft Palate Craniofac J 1995, 32:217-27. Publisher Full Text CrossRef
65. Lele S, Richtsmeier JT: / An invariant approach to the statistical analysis of shapes. London: Chapman and Hall/CRC Press; 2001. CrossRef
66. Wilkinson DG: / In situ hybridization: a practical approach. London, UK: Oxford University Press; 1992. - 作者单位：Yingli Wang (1)
Miao Sun (2) (3)
Victoria L Uhlhorn (1)
Xueyan Zhou (1)
Inga Peter (1)
Neus Martinez-Abadias (4)
Cheryl A Hill (4)
Christopher J Percival (4)
Joan T Richtsmeier (4) (5)
David L Huso (6)
Ethylin Wang Jabs (1) (2)
1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York, USA
2. Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
3. Department of Medical Genetics and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
4. Department of Anthropology, Pennsylvania State University, USA
5. Center for Functional Anatomy and Evolution, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
6. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
文摘
Background Apert syndrome is characterized by craniosynostosis and limb abnormalities and is primarily caused by FGFR2 +/P253R and +/S252W mutations. The former mutation is present in approximately one third whereas the latter mutation is present in two-thirds of the patients with this condition. We previously reported an inbred transgenic mouse model with the Fgfr2 +/S252W mutation on the C57BL/6J background for Apert syndrome. Here we present a mouse model for the Fgfr2+/P253R mutation. Results We generated inbred Fgfr2 +/P253R mice on the same C56BL/6J genetic background and analyzed their skeletal abnormalities. 3D micro-CT scans of the skulls of the Fgfr2 +/P253R mice revealed that the skull length was shortened with the length of the anterior cranial base significantly shorter than that of the Fgfr2 +/S252W mice at P0. The Fgfr2 +/P253R mice presented with synostosis of the coronal suture and proximate fronts with disorganized cellularity in sagittal and lambdoid sutures. Abnormal osteogenesis and proliferation were observed at the developing coronal suture and long bones of the Fgfr2 +/P253R mice as in the Fgfr2 +/S252W mice. Activation of mitogen-activated protein kinases (MAPK) was observed in the Fgfr2 +/P253R neurocranium with an increase in phosphorylated p38 as well as ERK1/2, whereas phosphorylated AKT and PKCα were not obviously changed as compared to those of wild-type controls. There were localized phenotypic and molecular variations among individual embryos with different mutations and among those with the same mutation. Conclusions Our in vivo studies demonstrated that the Fgfr2 +/P253R mutation resulted in mice with cranial features that resemble those of the Fgfr2 +/S252W mice and human Apert syndrome. Activated p38 in addition to the ERK1/2 signaling pathways may mediate the mutant neurocranial phenotype. Though Apert syndrome is traditionally thought to be a consistent phenotype, our results suggest localized and regional variations in the phenotypes that characterize Apert syndrome.