Craniosynostosis Molecular pathways and future pharmacologic therapy

Organogenesis

Volumn 8, Issue 4, 2012, Pages 103-113

  Senarath Yapa, Kshemendra ^a   Chung, Michael T ^a   McArdle, Adrian ^a   Wong, Victor W ^b   Quarto, Natalina ^b   Longaker, Michael T ^a   Wan, Derrick C ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Calvarium; Craniosynostosis; FGF; Signaling; Suture

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; EPHRIN; FIBROBLAST GROWTH FACTOR RECEPTOR; TRANSCRIPTION FACTOR MSX2; TRANSCRIPTION FACTOR TWIST;

ACROCEPHALOSYNDACTYLY; BONE DEVELOPMENT; BRAIN DEVELOPMENT; CRANIOFACIAL SYNOSTOSIS; DOWN REGULATION; DURA MATER; GENE EXPRESSION; HUMAN; MORPHOGENESIS; NONHUMAN; PATHOGENESIS; REVIEW; SIGNAL TRANSDUCTION; SKULL SUTURE; SURGICAL APPROACH;

CALVARIUM; CRANIOSYNOSTOSIS; FGF; SIGNALING; SUTURE;

ANIMALS; CRANIAL SUTURES; CRANIOSYNOSTOSES; DISEASE MODELS, ANIMAL; HUMANS; MOLECULAR TARGETED THERAPY; MORPHOGENESIS; SIGNAL TRANSDUCTION;

EID: 84874595852     PISSN: 15476278     EISSN: 15558592     Source Type: Journal    
DOI: 10.4161/org.23307     Document Type: Review

References (103)

1. Otto. A. Lehrbuch der Pathologischen Anatomie. Berlin, Germany: Rucher., 1830.
2. Lenton KA, Nacamuli RP, Wan DC, Helms JA, Longaker MT. Cranial suture biology. Curr Top Dev Biol 2005; 66:287-328; PMID:15797457; http:// dx.doi.org/10.1016/S0070-2153(05)66009-7.
3. Slater BJ, Lenton KA, Kwan MD, Gupta DM, Wan DC, Longaker MT. Cranial sutures: a brief review. Plast Reconstr Surg 2008; 121:170e-8e; PMID:18349596; http://dx.doi.org/10.1097/01.prs.0000304441.99483.97.
4. Virchow R. Berh Phyd Med Gesellsch Wuerzburg. 1851; 2:231-71.
5. Moss ML. The pathogenesis of premature cranial synostosis in man. Acta Anat (Basel) 1959; 37:351-70; PMID:14424622; http://dx.doi. org/10.1159/ 000141479.
6. Crouzon O. Dysostose cranio-faciale hereditaire. Bull Mem Soc Med Hop Paris 1912; 33:545-55.
7. Tessier P.Total facial osteotomy. Crouzon's syndrome, Apert's syndrome: oxycephaly, scaphocephaly, turricephaly]. Ann Chir Plast 1967; 12:273-86; PMID:5622570.
8. Tessier P. [The treatment of facial dysmorphy peculiary to cranio-facial dysostosis (C.F.D.). Crouzon and Apert diseases. Total osteotomy and sagittal displacement of the facial mass]. Chirurgie 1970; 96:667-74; PMID:5450453.
9. Grabb WC, Smith JW, Aston SJ. Plastic Surgery, 4th Edition. Boston: Little Brown, 1991.
10. Whitaker LA, Munro IR, Salyer KE, Jackson IT, Ortiz-Monasterio F, Marchac D. Combined report of problems and complications in 793 craniofacial operations. Plast Reconstr Surg 1979; 64:198-203; PMID:377338; http://dx.doi.org/10.1097/00006534- 197908000-00011.
11. Proctor MR. Endoscopic cranial suture release for the treatment of craniosynostosis-is it the future? J Craniofac Surg 2012; 23:225-8; PMID:22337414; http://dx.doi.org/10.1097/SCS.0b013e318241b8f6.
12. Marchac D, Renier D. New aspects of craniofacial surgery. World J Surg 1990; 14:725-32; PMID:2256344; http://dx.doi.org/10.1007/BF01670519.
13. McCarthy JG, Epstein F, Sadove M, Grayson B, Zide B. Early surgery for craniofacial synostosis: an 8-year experience. Plast Reconstr Surg 1984; 73:521-33; PMID:6709733; http://dx.doi. org/10.1097/00006534-198404000-00001.
14. Wilkie AO, Morriss-Kay GM. Genetics of craniofacial development and malformation. Nat Rev Genet 2001; 2:458-68; PMID:11389462; http://dx.doi. org/10.1038/35076601.
15. Noden DM. Interactions and fates of avian craniofacial mesenchyme. Development 1988; 103(Suppl):121-40; PMID:3074905.
16. Le Lièvre CS. Participation of neural crest-derived cells in the genesis of the skull in birds. J Embryol Exp Morphol 1978; 47:17-37; PMID:722230.
17. Couly GF, Coltey PM, Le Douarin NM. The triple origin of skull in higher vertebrates: a study in quailchick chimeras. Development 1993; 117:409-29; PMID:8330517.
18. 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; PMID:11784098; http://dx.doi.org/10.1006/ dbio.2001.0487.
19. 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; PMID:16313397; http:// dx.doi.org/10.1111/j. 1469-7580.2005.00475.x.
20. Cohen MM Jr., Craniosynostosis MR. Diagnosis, Evaluation and Management., 2nd Edition. Ed. New York.: Oxford University Press., 2000.
21. Rice DP. Craniofacial sutures. Development, disease and treatment. Preface. Front Oral Biol 2008; 12:xi; PMID:18491429.
22. Merrill AE, Bochukova EG, Brugger SM, Ishii M, Pilz DT, Wall SA, et al. Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Hum Mol Genet 2006; 15:1319-28; PMID:16540516; http://dx.doi. org/10.1093/hmg/ddl052.
23. Lattanzi W, Bukvic N, Barba M, Tamburrini G, Bernardini C, Michetti F, et al. Genetic basis of singlesuture synostoses: genes, chromosomes and clinical implications. Childs Nerv Syst 2012; 28:1301-10; PMID:22872241; http://dx.doi.org/10.1007/s00381- 012-1781-1.
24. Mefford HC, Shafer N, Antonacci F, Tsai JM, Park SS, Hing AV, et al. Copy number variation analysis in single-suture craniosynostosis: multiple rare variants including RUNX2 duplication in two cousins with metopic craniosynostosis. Am J Med Genet A 2010; 152A:2203-10; PMID:20683987; http://dx.doi. org/10.1002/ajmg.a.33557.
25. Cunningham ML, Horst JA, Rieder MJ, Hing AV, Stanaway IB, Park SS, et al. IGF1R variants associated with isolated single suture craniosynostosis. Am J Med Genet A 2011; 155A:91-7; PMID:21204214; http:// dx.doi.org/10.1002/ajmg.a. 33781.
26. Passos-Bueno MR, Serti Eacute AE, Jehee FS, Fanganiello R, Yeh E. Genetics of craniosynostosis: genes, syndromes, mutations and genotypephenotype correlations. Front Oral Biol 2008; 12:107-43; PMID:18391498; http://dx.doi. org/10.1159/000115035.
27. Givol DEV, Lonai P. The fibroblast growth factor signalling pathway. In: Epstein CJ ER, Wynshaw-Boris A., ed. Inborn errors of development. Oxford.: Oxford University Press., 2004.:367-79.
28. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 2005; 16:139-49; PMID:15863030; http:// dx.doi.org/10.1016/j.cytogfr.2005.01.001.
29. Wilkie AO, Slaney SF, Oldridge M, Poole MD, Ashworth GJ, Hockley AD, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 1995; 9:165-72; PMID:7719344; http://dx.doi.org/10. 1038/ng0295-165.
30. Robin NH, Feldman GJ, Mitchell HF, Lorenz P, Wilroy RS, Zackai EH, et al. Linkage of Pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity. Hum Mol Genet 1994; 3:2153-8; PMID:7881412; http://dx.doi.org/10.1093/ hmg/3.12.2153.
31. Muenke M, Gripp KW, McDonald-McGinn DM, Gaudenz K, Whitaker LA, Bartlett SP, et al. A unique point mutation in the fibroblast growth factor receptorgene (FGFR3) defines a new craniosynostosis syndrome. Am J Hum Genet 1997; 60:555-64; PMID:9042914.
32. Patel A, Terner J, Travieso R, Clune JE, Steinbacher D, Persing JA. On Bernard Sarnat's 100th birthday: pathology and management of craniosynostosis. J Craniofac Surg 2012; 23:105-12; PMID:22337384; http://dx.doi.org/10.1097/SCS. 0b013e318240fb0d.
33. Reid CS, McMorrow LE, McDonald-McGinn DM, Grace KJ, Ramos FJ, Zackai EH, et al. Saethre- Chotzen syndrome with familial translocation at chromosome 7p22. Am J Med Genet 1993; 47:637- 9; PMID:8266989; http://dx.doi.org/10.1002/ ajmg.1320470511.
34. Wilkie AO, Yang SP, Summers D, Poole MD, Reardon W, Winter RM. Saethre-Chotzen syndrome associated with balanced translocations involving 7p21: three further families. J Med Genet 1995; 32:174- 80; PMID:7783164; http://dx.doi.org/10.1136/ jmg.32.3.174.
35. Gripp KW, Zackai EH, Stolle CA. Mutations in the human TWIST gene. Hum Mutat 2000; 15:479; PMID:10790211; http://dx.doi.org/10.1002/ (SICI)1098-1004(200005)15:5479::AIDHUMU11 3.0.CO;2-X.
36. Cunningham ML, Seto ML, Ratisoontorn C, Heike CL, Hing AV. Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofac Res 2007; 10:67-81; PMID:17552943; http://dx.doi. org/10.1111/j.1601-6343.2007.00389.x.
37. Jabs EW. A TWIST in the fate of human osteoblasts identifies signaling molecules involved in skull development. J Clin Invest 2001; 107:1075- 7; PMID:11342569; http://dx.doi.org/10.1172/ JCI12853.
38. Lee MS, Lowe GN, Strong DD, Wergedal JE, Glackin CA. TWIST, a basic helix-loop-helix transcription factor, can regulate the human osteogenic lineage. J Cell Biochem 1999; 75:566-77; PMID:10572240; http : // dx.d o i . o r g / 1 0 . 1 0 0 2 / (S I C I) 1 0 9 7 - 4644(19991215)75:4566::AID-JCB33.0. CO;2-0.
39. Ignelzi MA Jr., Wang W, Young AT. Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. J Bone Miner Res 2003; 18:751- 9; PMID:12674336; http://dx.doi.org/10.1359/ jbmr.2003.18.4.751.
40. Liu YH, Tang Z, Kundu RK, Wu L, Luo W, Zhu D, et al. Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans. Dev Biol 1999; 205:260-74; PMID:9917362; http://dx.doi. org/10.1006/dbio.1998.9114.
41. Liu YH, Kundu R, Wu L, Luo W, Ignelzi MA Jr., Snead ML, et al. Premature suture closure and ectopic cranial bone in mice expressing Msx2 transgenes in the developing skull. Proc Natl Acad Sci U S A 1995; 92:6137-41; PMID:7597092; http://dx.doi. org/10.1073/pnas.92.13.6137.
42. Müller U, Steinberger D, Kunze S. Molecular genetics of craniosynostotic syndromes. Graefes Arch Clin Exp Ophthalmol 1997; 235:545-50; PMID:9342602; http://dx.doi.org/10.1007/BF00947081.
43. Twigg SR, Kan R, Babbs C, Bochukova EG, Robertson SP, Wall SA, et al. Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc Natl Acad Sci U S A 2004; 101:8652-7; PMID:15166289; http://dx.doi. org/10.1073/pnas.0402819101.
44. Wieland I, Jakubiczka S, Muschke P, Cohen M, Thiele H, Gerlach KL, et al. Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet 2004; 74:1209-15; PMID:15124102; http://dx.doi. org/10.1086/421532.
45. Zafeiriou DI, Pavlidou EL, Vargìami E. Diverse clinical and genetic aspects of craniofrontonasal syndrome. Pediatr Neurol 2011; 44:83-7; PMID:21215906; http:// dx.doi.org/10.1016/j.pediatrneurol.2010.10.012.
46. Jenkins D, Baynam G, De Catte L, Elcioglu N, Gabbett MT, Hudgins L, et al. Carpenter syndrome: extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay. Hum Mutat 2011; 32:E2069-78; PMID:21412941; http://dx.doi. org/10.1002/humu.21457.
47. Thomas JT, Lin K, Nandedkar M, Camargo M, Cervenka J, Luyten FP. A human chondrodysplasia due to a mutation in a TGF-beta superfamily member. Nat Genet 1996; 12:315-7; PMID:8589725; http://dx.doi. org/10.1038/ng0396-315.
48. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005; 37:275-81; PMID:15731757; http:// dx.doi.org/10.1038/ng1511.
49. Roth DA, Gold LI, Han VK, McCarthy JG, Sung JJ, Wisoff JH, et al. Immunolocalization of transforming growth factor beta 1, beta 2, and beta 3 and insulin-like growth factor I in premature cranial suture fusion. Plast Reconstr Surg 1997; 99:300- 9, discussion 310-6; PMID:9030135; http://dx.doi. org/10.1097/00006534-199702000-00002.
50. Opperman LA, Galanis V, Williams AR, Adab K. Transforming growth factor-beta3 (Tgf-beta3) downregulates Tgf-beta3 receptor type I (Tbetar-I) during rescue of cranial sutures from osseous obliteration. Orthod Craniofac Res 2002; 5:5-16; PMID:12071374; http://dx.doi.org/10.1034/j.1600-0544.2002.01179. x.
51. Opperman LA. Cranial sutures as intramembranous bone growth sites. Dev Dyn 2000; 219:472-85; PMID:11084647; http://dx.doi. org/10.1002/1097-0177(2000) 9999:9999::AIDDVDY1073> 3.0.CO;2-F.
52. Sahar DE, Longaker MT, Quarto N. Soxi neural crest determinant gene controls patterning and closure of the posterior frontal cranial suture. Dev Biol 2005; 280:344-61; PMID:15882577; http://dx.doi. org/10.1016/j.ydbio.2005. 01.022.
53. Greenwald JA, Mehrara BJ, Spector JA, Warren SM, Fagenholz PJ, Smith LE, et al. In vivo modulation of FGF biological activity alters cranial suture fate. Am J Pathol 2001; 158:441-52; PMID:11159182; http:// dx.doi.org/10.1016/S0002- 9440(10)63987-9.
54. James AW, Xu Y, Wang R, Longaker MT. Proliferation, osteogenic differentiation, and fgf-2 modulation of posterofrontal/sagittal suture-derived mesenchymal cells in vitro. Plast Reconstr Surg 2008; 122:53- 63;PMID:18594386; http://dx.doi.org/10.1097/ PRS.0b013e31817747b5.
55. Mehrara BJ, Spector JA, Greenwald JA, Ueno H, Longaker MT. Adenovirus-mediated transmission of a dominant negative transforming growth factor-beta receptor inhibits in vitro mouse cranial suture fusion. Plast Reconstr Surg 2002; 110:506-14; PMID:12142669; http://dx.doi. org/10.1097/00006534-200208000-00022.
56. James AW, Xu Y, Lee JK, Wang R, Longaker MT. Differential effects of TGF-beta1 and TGF-beta3 on chondrogenesis in posterofrontal cranial suturederived mesenchymal cells in vitro. Plast Reconstr Surg 2009; 123:31-43; PMID:19116522; http://dx.doi. org/10.1097/PRS.0b013e3181904c19.
57. Kim HJ, Rice DP, Kettunen PJ, Thesleff I. FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development 1998; 125:1241-51; PMID:9477322.
58. nature01545.
59. Behr B, Longaker MT, Quarto N. Differential activation of canonical Wnt signaling determines cranial sutures fate: a novel mechanism for sagittal suture craniosynostosis. Dev Biol 2010; 344:922- 40; PMID:20547147; http://dx.doi.org/10.1016/j. ydbio.2010.06.009.
60. Jacob S, Wu C, Freeman TA, Koyama E, Kirschner RE. Expression of Indian Hedgehog, BMP-4 and Noggin in craniosynostosis induced by fetal constraint. Ann Plast Surg 2007; 58:215-21; PMID:17245153; http:// dx.doi.org/10.1097/01.sap. 0000232833.41739.a5.
61. Persing JEM, James HE. Scientific foundations and surgical treatment of craniosynostosis. In: Moffett. LK-MaB, ed. Sutures and intruterine deformation. Baltimore.: Williams and Wilkins., 1989.96-106.
62. Mooney MP, Losken HW, Tschakaloff A, Siegel MI, Losken A, Lalikos JF. Congenital bilateral coronal suture synostosis in a rabbit and craniofacial growth comparisons with experimental models. Cleft Palate Craniofac J 1993; 30:121-8; PMID:8452830; http:// dx.doi.org/10.1597/1545-1569(1993)0300121:CBC SSI2.3.CO;2.
63. Mooney MP, Losken HW, Siegel MI, Lalikos JF, Losken A, Smith TD, et al. Development of a strain of rabbits with congenital simple nonsyndromic coronal suture synostosis. Part I: Breeding demographics, inheritance pattern, and craniofacial anomalies. Cleft Palate Craniofac J 1994; 31:1-7; PMID:8130237; http:// dx.doi.org/10.1597/1545-1569(1994)0310001:DOA SOR2.3.CO;2.
64. Mooney MP, Siegel MI, Burrows AM, Smith TD, Losken HW, Dechant J, et al. A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. II. Intracranial contents, intracranial volume, and intracranial pressure. Childs Nerv Syst 1998; 14:247- 55; PMID:9694336; http://dx.doi.org/10.1007/ s003810050220.
65. Mooney MP, Aston CE, Siegel MI, Losken HW, Smith TD, Burrows AM, et al. Craniosynostosis with autosomal dominant transmission in New Zealand white rabbits. J Craniofac Genet Dev Biol 1996; 16:52-63; PMID:8675615.
66. Mooney MP, Burrows AM, Smith TD, Losken HW, Opperman LA, Dechant J, et al. Correction of coronal suture synostosis using suture and dura mater allografts in rabbits with familial craniosynostosis. Cleft Palate Craniofac J 2001; 38:206-25; PMID:11386428; http:// dx.doi.org/10.1597/1545-1569(2001) 0380206:COC SSU>2.0.CO;2.
67. Sheehan-Rooney K, Pálinkášová B, Eberhart JK, Dixon MJ. A cross-species analysis of Satb2 expression suggests deep conservation across vertebrate lineages. Dev Dyn 2010; 239:3481-91; PMID:21089028; http:// dx.doi.org/10.1002/dvdy.22483.
68. Quarto N, Longaker MT. The zebrafish (Danio rerio): a model system for cranial suture patterning. Cells Tissues Organs 2005; 181:109-18; PMID:16534205; http://dx.doi.org/10.1159/000091100.
69. Slater BJ, Liu KJ, Kwan MD, Quarto N, Longaker MT. Cranial osteogenesis and suture morphology in Xenopus laevis: a unique model system for studying craniofacial development. PLoS One 2009; 4:e3914; PMID:19156194; http://dx.doi.org/10.1371/journal. pone.0003914.
70. Slater BJ, Kwan MD, Gupta DM, Lee JK, Longaker MT. The role of regional posterior frontal dura mater in the overlying suture morphology. Plast Reconstr Surg 2009; 123:463-9; PMID:19182602; http://dx.doi. org/10.1097/PRS. 0b013e3181954d21.
71. Roth DA, Bradley JP, Levine JP, McMullen HF, McCarthy JG, Longaker MT. Studies in cranial suture biology: part II. Role of the dura in cranial suture fusion. Plast Reconstr Surg 1996; 97:693-9; PMID:8628762; http://dx.doi.org/10. 1097/00006534-199604000- 00001.
72. Bradley JP, Levine JP, McCarthy JG, Longaker MT. Studies in cranial suture biology: regional dura mater determines in vitro cranial suture fusion. Plast Reconstr Surg 1997; 100:1091-9, 1100-2; PMID:9326769; http://dx.doi.org/ 10.1097/00006534-199710000- 00001.
73. Opperman LA, Sweeney TM, Redmon J, Persing JA, Ogle RC. Tissue interactions with underlying dura mater inhibit osseous obliteration of developing cranial sutures. Dev Dyn 1993; 198:312-22; PMID:8130378; http://dx.doi.org/10.1002/aja.1001980408.
74. Cooper GM, Durham EL, Cray JJ Jr., Siegel MI, Losee JE, Mooney MP. Tissue interactions between craniosynostotic dura mater and bone. J Craniofac Surg 2012; 23:919-24; PMID:22627405; http://dx.doi. org/10.1097/SCS.0b013e31824e645f.
75. Barone CM, Jimenez DF. Endoscopic craniectomy for early correction of craniosynostosis. Plast Reconstr Surg 1999; 104:1965-73, discussion 1974-5; PMID:11149758; http://dx.doi. org/10.1097/00006534-199912000-00003.
76. Ueno H, Gunn M, Dell K, Tseng A Jr., Williams L. A truncated form of fibroblast growth factor receptorinhibits signal transduction by multiple types of fibroblast growth factor receptor. J Biol Chem 1992; 267:1470-6; PMID:1309784.
77. 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- 50; PMID:17694057; http://dx.doi.org/10.1038/ ng2096.
78. Lomri A, Lemonnier J, Delannoy P, Marie PJ. Increased expression of protein kinase Calpha, interleukin-alpha, and RhoA guanosine 5'-triphosphatase in osteoblasts expressing the Ser252Trp fibroblast growth factor 2 receptor Apert mutation: identification by analysis of complementary DNA microarray. J Bone Miner Res 2001; 16:705-12; PMID:11315998; http:// dx.doi.org/10.1359/jbmr. 2001.16.4.705.
79. Kim HJ, Lee MH, Park HS, Park MH, Lee SW, Kim SY, et al. Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated premature cranial suture closure. Dev Dyn 2003; 227:335-46; PMID:12815619; http://dx.doi.org/10. 1002/dvdy.10319.
80. Opperman LA, Adab K, Gakunga PT. Transforming growth factor-beta 2 and TGF-beta 3 regulate fetal rat cranial suture morphogenesis by regulating rates of cell proliferation and apoptosis. Dev Dyn 2000; 219:237-47; PMID:11002343; http://dx.doi. org/10.1002/1097-0177(2000)9999:9999::AIDDVDY1044 3.0.CO;2-F.
81. Opperman LA, Chhabra A, Cho RW, Ogle RC. Cranial suture obliteration is induced by removal of transforming growth factor (TGF)-beta 3 activity and prevented by removal of TGF-beta 2 activity from fetal rat calvaria in vitro. J Craniofac Genet Dev Biol 1999; 19:164-73; PMID:10589398.
82. Ko SH, Behr B, Longaker MT. Discussion. TGFbeta1 RNA interference in mouse primary dura cell culture: downstream effects on TGF receptors, FGF- 2, and FGF-R1 mRNA levels. Plast Reconstr Surg 2009; 124:1474-6; PMID:20009833; http://dx.doi. org/10.1097/PRS.0b013e3181b989de.
83. Gosain AK, Machol JA 4th, Gliniak C, Halligan NL. TGF-beta1 RNA interference in mouse primary dura cell culture: downstream effects on TGF receptors, FGF-2, and FGF-R1 mRNA levels. Plast Reconstr Surg 2009; 124:1466-73; PMID:20009832; http://dx.doi. org/10.1097/PRS.0b013e3181b98947.
84. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 2009; 8:129-38; PMID:19180106; http://dx.doi.org/10.1038/nrd2742.
85. Cooper GM, Usas A, Olshanski A, Mooney MP, Losee JE, Huard J. Ex vivo Noggin gene therapy inhibits bone formation in a mouse model of postoperative resynostosis. Plast Reconstr Surg 2009; 123(Suppl):94S-PMID:19182668; http://dx.doi.org/10.1097/ PRS.0b013e318191c05b.
86. Cooper GM, Curry C, Barbano TE, Burrows AM, Vecchione L, Caccamese JF, et al.Noggin inhibits postoperative resynostosis in craniosynostotic rabbits. J Bone Miner Res 2007; 22:1046-54; PMID:17437358; http://dx.doi.org/10.1359/jbmr. 070410.
87. Lajeunie E, Heuertz S, El Ghouzzi V, Martinovic J, Renier D, Le Merrer M, et al. Mutation screening in patients with syndromic craniosynostoses indicates that a limited number of recurrent FGFR2 mutations accounts for severe forms of Pfeiffer syndrome. Eur J Hum Genet 2006; 14:289-98; PMID:16418739; http://dx.doi.org/10.1038/sj.ejhg.5201558.
88. Rossi M, Jones RL, Norbury G, Bloch-Zupan A, Winter RM. The appearance of the feet in Pfeiffer syndrome caused by FGFR1 P252R mutation. Clin Dysmorphol 2003; 12:269-74; PMID:14564217; http://dx.doi.org/10.1097/00019605-200310000- 00012.
89. Muenke M, Schell U, Hehr A, Robin NH, Losken HW, Schinzel A, et al. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet 1994; 8:269-74; PMID:7874169; http://dx.doi.org/10.1038/ ng1194-269.
90. Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet 1994; 8:98-103; PMID:7987400; http://dx.doi. org/10.1038/ng0994-98.
91. Slaney SF, Oldridge M, Hurst JA, Moriss-Kay GM, Hall CM, Poole MD, et al. Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome. Am J Hum Genet 1996; 58:923-32; PMID:8651276.
92. Bochukova EG, Roscioli T, Hedges DJ, Taylor IB, Johnson D, David DJ, et al. Rare mutations of FGFR2 causing apert syndrome: identification of the first partial gene deletion, and an Alu element insertion from a new subfamily. Hum Mutat 2009; 30:204- 11; PMID:18726952; http://dx.doi.org/10.1002/ humu.20825.
93. Ibrahimi OA, Chiu ES, McCarthy JG, Mohammadi M. Understanding the molecular basis of Apert syndrome. Plast Reconstr Surg 2005; 115:264-70; PMID:15622262.
94. Cornejo-Roldan LR, Roessler E, Muenke M. Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. Hum Genet 1999; 104:425- 31; PMID:10394936; http://dx.doi.org/10.1007/ s004390050979.
95. Rutland P, Pulleyn LJ, Reardon W, Baraitser M, Hayward R, Jones B, et al. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet 1995; 9:173-6; PMID:7719345; http://dx.doi.org/10.1038/ ng0295- 173.
96. Slavotinek A, Crawford H, Golabi M, Tao C, Perry H, Oberoi S, et al. Novel FGFR2 deletion in a patient with Beare-Stevenson-like syndrome. Am J Med Genet A 2009; 149A:1814-7; PMID:19610084; http://dx.doi. org/10.1002/ajmg.a. 32947.
97. Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet 1995; 11:462-4; PMID:7493034; http://dx.doi.org/10.1038/ng1295- 462.
98. Agochukwu NB, Solomon BD, Gropman AL, Muenke M. Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis. Pediatr Neurol 2012; 47:355-61; PMID:23044018; http://dx.doi.org/10.1016/j.pediatrneurol. 2012.07.004.
99. Doherty ES, Lacbawan F, Hadley DW, Brewer C, Zalewski C, Kim HJ, et al. Muenke syndrome (FGFR3- related craniosynostosis): expansion of the phenotype and review of the literature. Am J Med Genet A 2007; 143A:3204-15; PMID:18000976; http://dx.doi. org/10.1002/ajmg.a.32078.
100. Jin M, Yu Y, Qi H, Xie Y, Su N, Wang X, et al. A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia. Hum Mol Genet 2012; 21:5443-55; PMID:23014564; http://dx.doi. org/10.1093/hmg/dds390. ©2012 Landes Bioscience. Do not distribute.
101. Wallis D, Lacbawan F, Jain M, Der Kaloustian VM, Steiner CE, Moeschler JB, et al. Additional EFNB1 mutations in craniofrontonasal syndrome. Am J Med Genet A 2008; 146A:2008-12; PMID:18627045; http://dx.doi.org/10.1002/ajmg.a. 32388.
102. Bonaventure J, El Ghouzzi V. Molecular and cellular bases of syndromic craniosynostoses. Expert Rev Mol Med 2003; 5:1-17; PMID:14987407; http://dx.doi. org/10.1017/S1462399403005751.
103. Foo R, Guo Y, McDonald-McGinn DM, Zackai EH, Whitaker LA, Bartlett SP. The natural history of patients treated for TWIST1-confirmed Saethre- Chotzen syndrome. Plast Reconstr Surg 2009; 124:2085-95; PMID:19952666; http://dx.doi. org/10.1097/PRS.0b013e3181bf83ce.