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Hand in glove: brain and skull in development and dysmorphogenesis

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Abstract

The brain originates relatively early in development from differentiated ectoderm that forms a hollow tube and takes on an exceedingly complex shape with development. The skull is made up of individual bony elements that form from neural crest- and mesoderm-derived mesenchyme that unite to provide support and protection for soft tissues and spaces of the head. The meninges provide a protective and permeable membrane between brain and skull. Across evolutionary and developmental time, dynamic changes in brain and skull shape track one another so that their integration is evidenced in two structures that fit soundly regardless of changes in biomechanical and physiologic functions. Evidence for this tight correspondence is also seen in diseases of the craniofacial complex that are often classified as diseases of the skull (e.g., craniosynostosis) or diseases of the brain (e.g., holoprosencephaly) even when both tissues are affected. Our review suggests a model that links brain and skull morphogenesis through coordinated integration of signaling pathways (e.g., FGF, TGFβ, Wnt) via processes that are not currently understood, perhaps involving the meninges. Differences in the earliest signaling of biological structure establish divergent designs that will be enhanced during morphogenesis. Signaling systems that pattern the developing brain are also active in patterning required for growth and assembly of the skull and some members of these signaling families have been indicated as causal for craniofacial diseases. Because cells of early brain and skull are sensitive to similar signaling families, variation in the strength or timing of signals or shifts in patterning boundaries that affect one system (neural or skull) could also affect the other system and appropriate co-adjustments in development would be made. Interactions of these signaling systems and of the tissues that they pattern are fundamental to the consistent but labile functional and structural association of brain and skull conserved over evolutionary time obvious in the study of development and disease.

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References

  1. Aarden EM, Burger EH, Nijweide PJ (1994) Function of osteocytes in bone. J Cell Biochem 55(3):287–299

    Article  PubMed  CAS  Google Scholar 

  2. Aldridge K, Hill CA, Austin JR, Percival C, Martinez-Abadias N, Neuberger T, Wang Y, Jabs EW, Richtsmeier JT (2010) Brain phenotypes in two FGFR2 mouse models for Apert syndrome. Dev Dyn 239(3):987–997

    Article  PubMed  CAS  Google Scholar 

  3. Aldridge K, Kane AA, Marsh JL, Panchal J, Boyadjiev SA, Yan P, Govier D, Ahmad W, Richtsmeier JT (2005) Brain morphology in nonsyndromic unicoronal craniosynostosis. Anat Rec Part A 285A(2):690–698

    Article  Google Scholar 

  4. Aldridge K, Marsh J, Govier D, Richtsmeier J (2002) Central nervous system phenotypes in craniosynostosis. J Anat 201(1):31–39

    Article  PubMed  Google Scholar 

  5. Allen HL, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, Willer CJ, Jackson AU, Vedantam S, Raychaudhuri S, Ferreira T, Wood AR, Weyant RJ, Segre AV, Speliotes EK, Wheeler E, Soranzo N, Park JH, Yang J, Gudbjartsson D, Heard-Costa NL, Randall JC, Qi L, Smith AV, Magi R, Pastinen T, Liang L, Heid IM, Luan J, Thorleifsson G, Winkler TW, Goddard ME, Lo KS, Palmer C, Workalemahu T, Aulchenko YS, Johansson A, Zillikens MC, Feitosa MF, Esko T, Johnson T, Ketkar S, Kraft P, Mangino M, Prokopenko I, Absher D, Albrecht E, Ernst F, Glazer NL, Hayward C, Hottenga JJ, Jacobs KB, Knowles JW, Kutalik Z, Monda KL, Polasek O, Preuss M, Rayner NW, Robertson NR, Steinthorsdottir V, Tyrer JP, Voight BF, Wiklund F, Xu JF, Zhao JH, Nyholt DR, Pellikka N, Perola M, Perry JRB, Surakka I, Tammesoo ML, Altmaier EL, Amin N, Aspelund T, Bhangale T, Boucher G, Chasman DI, Chen C, Coin L, Cooper MN, Dixon AL, Gibson Q, Grundberg E, Hao K, Junttila MJ, Kaplan LM, Kettunen J, Konig IR, Kwan T, Lawrence RW, Levinson DF, Lorentzon M, McKnight B, Morris AP, Muller M, Ngwa JS, Purcell S, Rafelt S, Salem RM, Salvi E, Sanna S, Shi JX, Sovio U, Thompson JR, Turchin MC, Vandenput L, Verlaan DJ, Vitart V, White CC, Ziegler A, Almgren P, Balmforth AJ, Campbell H, Citterio L, De Grandi A, Dominiczak A, Duan J, Elliott P, Elosua R, Eriksson JG, Freimer NB, Geus EJC, Glorioso N, Haiqing S, Hartikainen AL, Havulinna AS, Hicks AA, Hui JN, Igl W, Illig T, Jula A, Kajantie E, Kilpelaeinen TO, Koiranen M, Kolcic I, Koskinen S, Kovacs P, Laitinen J, Liu JJ, Lokki ML, Marusic A, Maschio A, Meitinger T, Mulas A, Pare G, Parker AN, Peden JF, Petersmann A, Pichler I, Pietilainen KH, Pouta A, Riddertrale M, Rotter JI, Sambrook JG, Sanders AR, Schmidt CO, Sinisalo J, Smit JH, Stringham HM, Walters GB, Widen E, Wild SH, Willemsen G, Zagato L, Zgaga L, Zitting P, Alavere H, Farrall M, McArdle WL, Nelis M, Peters MJ, Ripatti S, Meurs JBJ, Aben KK, Ardlie KG, Beckmann JS, Beilby JP, Bergman RN, Bergmann S, Collins FS, Cusi D, den Heijer M, Eiriksdottir G, Gejman PV, Hall AS, Hamsten A, Huikuri HV, Iribarren C, Kahonen M, Kaprio J, Kathiresan S, Kiemeney L, Kocher T, Launer LJ, Lehtimaki T, Melander O, Mosley TH, Musk AW, Nieminen MS, O'Donnell CJ, Ohlsson C, Oostra B, Palmer LJ, Raitakari O, Ridker PM, Rioux JD, Rissanen A, Rivolta C, Schunkert H, Shuldiner AR, Siscovick DS, Stumvoll M, Tonjes A, Tuomilehto J, van Ommen GJ, Viikari J, Heath AC, Martin NG, Montgomery GW, Province MA, Kayser M, Arnold AM, Atwood LD, Boerwinkle E, Chanock SJ, Deloukas P, Gieger C, Gronberg H, Hall P, Hattersley AT, Hengstenberg C, Hoffman W, Lathrop GM, Salomaa V, Schreiber S, Uda M, Waterworth D, Wright AF, Assimes TL, Barroso I, Hofman A, Mohlke KL, Boomsma DI, Caulfield MJ, Cupples LA, Erdmann J, Fox CS, Gudnason V, Gyllensten U, Harris TB, Hayes RB, Jarvelin MR, Mooser V, Munroe PB, Ouwehand WH, Penninx BW, Pramstaller PP, Quertermous T, Rudan I, Samani NJ, Spector TD, Volzke H, Watkins H, Wilson JF, Groop LC, Haritunians T, Hu FB, Kaplan RC, Metspalu A, North KE, Schlessinger D, Wareham NJ, Hunter DJ, O'Connell JR, Strachan DP, Schadt HE, Thorsteinsdottir U, Peltonen L, Uitterlinden AG, Visscher PM, Chatterjee N, Loos RJF, Boehnke M, McCarthy MI, Ingelsson E, Lindgren CM, Abecasis GR, Stefansson K, Frayling TM, Hirschhorn JN, Consortium P (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nat 467(7317):832-838

    Google Scholar 

  6. Baker CVH, Bronner-Fraser M (2001) Vertebrate cranial placodes I. Embryonic induction. Dev Biol 232(1):1–61

    Article  PubMed  CAS  Google Scholar 

  7. Bidwell JP, Pavalko FM (2010) The load-bearing mechanosome revisited. Clin Rev Bone Miner Metab 8:213–223

    Article  PubMed  Google Scholar 

  8. Buchanan AV, Sholtis S, Richtsmeier J, Weiss KM (2009) What are genes “for” or where are traits “from”? What is the question? Bioessays 31(2):198–208

    Article  PubMed  Google Scholar 

  9. Carroll S (2001) From DNA to diversity: molecular genetics and the evolution of animal design. Blackwell, Oxford

    Google Scholar 

  10. Case N, Ma MY, Sen B, Xie ZH, Gross TS, Rubin J (2008) Beta-catenin levels influence rapid mechanical responses in osteoblasts. J Biol Chem 283(43):29196–29205

    Article  PubMed  CAS  Google Scholar 

  11. Cavodeassi F, Houart C (2012) Brain regionalization: of signaling centers and boundaries. Dev Neurobiol 72(3):218–233

    Article  PubMed  Google Scholar 

  12. Cayuso J, Marti E (2005) Morphogens in motion: growth control of the neural tube. J Neurobiol 64(4):376–387

    Article  PubMed  Google Scholar 

  13. Chizhikov VV, Millen KJ (2004) Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. J Neurosci 24(25):5694–5703

    Article  PubMed  CAS  Google Scholar 

  14. Cohen MJ, MacLean R (eds) (2000) Craniosynostosis: diagnosis, evaluation, and management. Oxford University Press, New York

    Google Scholar 

  15. Cohen MM (2006) Holoprosencephaly: clinical, anatomic, and molecular dimensions. Birth Defects Res A Clin Mol Teratol 76(9):658–673

    Article  PubMed  CAS  Google Scholar 

  16. Colas JF, Schoenwolf GC (2001) Towards a cellular and molecular understanding of neurulation. Dev Dyn 221(2):117–145

    Article  PubMed  CAS  Google Scholar 

  17. Colnot C, Lu CY, Hu D, Helms JA (2004) Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol 269(1):55–69

    Article  PubMed  CAS  Google Scholar 

  18. Cordero DR, Brugmann S, Chu YN, Bajpai R, Jame M, Helms JA (2011) Cranial neural crest cells on the move: their roles in craniofacial development. Am J Med Genet A 155A(2):270–279. doi:10.1002/Ajmg.A.33702

    PubMed  Google Scholar 

  19. Croce JC, McClay DR (2008) Evolution of the Wnt pathways. Methods Mol Biol (Clifton, NJ) 469:3–18

    Article  CAS  Google Scholar 

  20. Cunningham ML, Seto ML, Ratisoontorn C, Heike CL, Hing AV (2007) Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofac Res 10(2):67–81

    Article  PubMed  Google Scholar 

  21. Dailey L, Ambrosetti D, Mansukhani A, Basilico C (2005) Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev 16(2):233–247

    Article  PubMed  CAS  Google Scholar 

  22. Dehal P, Boore JL (2005) Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol 3(10):e314

    Article  PubMed  CAS  Google Scholar 

  23. Dennis J, Kurosaka H, Iulianella A, Pace J, Thomas N, Beckham S, Williams T, Trainor P (2012) Mutations in Hedgehog acyltransferase (Hhat) perturb hedgehog signaling, resulting in severe acrania-holoprosencephaly-agnathia craniofacial defects. PLoS Genet 8(10):e1002927

    Article  PubMed  CAS  Google Scholar 

  24. Donoghue PCJ, Graham A, Kelsh RN (2008) The origin and evolution of the neural crest. Bioessays 30(6):530–541

    Article  PubMed  Google Scholar 

  25. Dupin E, Sommer L (2012) Neural crest progenitors and stem cells: from early development to adulthood. Dev Biol 366(1):83–95

    Article  PubMed  CAS  Google Scholar 

  26. Engin FZ, Yao ZQ, Yang T, Zhou G, Bertin T, Jiang MM, Chen YQ, Wang L, Zheng H, Sutton RE, Boyce BF, Lee B (2008) Dimorphic effects of Notch signaling in bone homeostasis. Nat Med 14(3):299–305

    Article  PubMed  CAS  Google Scholar 

  27. Eswarakumar VP, Lax I, Schlessinger J (2005) Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 16(2):139–149

    Article  PubMed  CAS  Google Scholar 

  28. Fearon JA, McLaughlin EB, Kolar JC (2006) Sagittal craniosynostosis: surgical outcomes and long-term growth. Plast Reconstr Surg 117(2):532–541

    Article  PubMed  CAS  Google Scholar 

  29. Fong KD, Warren SM, Loboa EG, Henderson JH, Fang TD, Cowan CM, Carter DR, Longaker MT (2003) Mechanical strain affects dura mater biological processes: implications for immature calvarial healing. Plast Reconstr Surg 112(5):1312–1327

    Article  PubMed  Google Scholar 

  30. Franz-Odendaal TA, Hall BK, Witten PE (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235(1):176–190

    Article  PubMed  CAS  Google Scholar 

  31. Gagan JR, Tholpady SS, Ogle RC (2007) Cellular dynamics and tissue interactions of the dura mater during head development. Birth Defects Res C Embryo Today 81(4):297–304

    Article  PubMed  CAS  Google Scholar 

  32. Galliot B, Quiquand M, Ghila L, de Rosa R, Miljkovic-Licina M, Chera S (2009) Origins of neurogenesis, a cnidarian view. Dev Biol 332(1):2–24

    Article  PubMed  CAS  Google Scholar 

  33. Gans C, Northcutt RG (1983) Neural crest and the origin of vertebrates: a new head. Science 220(4594):268–273

    Article  PubMed  CAS  Google Scholar 

  34. Greenwald JA, Mehrara BJ, Spector JA, Chin GS, Steinbrech DS, Saadeh PB, Luchs JS, Paccione MF, Gittes GK, Longaker MT (2000) Biomolecular mechanisms of calvarial bone induction: immature versus mature dura mater. Plast Reconstr Surg 105(4):1382–1392

    PubMed  CAS  Google Scholar 

  35. Greenwald JA, Mehrara BJ, Spector JA, Fagenholz PJ, Saadeh PB, Steinbrech DS, Gittes GK, Longaker MT (2000) Immature versus mature dura mater: II. Differential expression of genes important to calvarial reossification. Plast Reconstr Surg 106(3):630–638

    PubMed  CAS  Google Scholar 

  36. Gross JB, Hanken J (2008) Review of fate-mapping studies of osteogenic cranial neural crest in vertebrates. Dev Biol 317(2):389–400

    Article  PubMed  CAS  Google Scholar 

  37. Guillemot F, Zimmer C (2011) From cradle to grave: the multiple roles of fibroblast growth factors in neural development. Neuron 71(4):574–588

    Article  PubMed  CAS  Google Scholar 

  38. Hajihosseini MK (2008) Fibroblast growth factor signaling in cranial suture development and pathogenesis. Front Oral Biol 12:160–177

    Article  PubMed  Google Scholar 

  39. Hall B (1999) The neural crest in development and evolution. Springer, New York

    Book  Google Scholar 

  40. Hall B (2005) Bones and cartilage: developmental and evolutionary skeletal biology. Elsevier, San Diego

    Google Scholar 

  41. Hall BK, Miyake T (2000) All for one and one for all: condensations and the initiation of skeletal development. Bioessays 22(2):138–147

    Article  PubMed  CAS  Google Scholar 

  42. Hanken J, Thorogood P (1993) Evolution and development of the vertebrate skull—the role of pattern-formation. Trends Ecol Evol 8(1):9–15

    Article  PubMed  CAS  Google Scholar 

  43. Hebert JM (2011) FGFs: neurodevelopment’s Jack-of-all-trades—how do they do it? Frontiers Neurosci 5:133

    Google Scholar 

  44. Henderson JH, Chang LY, Song HM, Longaker MT, Carter DR (2005) Age-dependent properties and quasi-static strain in the rat sagittal suture. J Biomech 38(11):2294–2301

    Article  PubMed  Google Scholar 

  45. Henderson JH, Nacamuli RP, Zhao B, Longaker MT, Carter DR (2005) Age-dependent residual tensile strains are present in the dura mater of rats. J R Soc Interface 2(3):159–167

    Article  PubMed  Google Scholar 

  46. Herring S (2008) Mechanical influences on suture development and patency. Front Oral Biol 12:41–56

    Article  PubMed  Google Scholar 

  47. Heuzé Y, Boyadjiev SA, Marsh JL, Kane AA, Cherkez E, Boggan JE, Richtsmeier JT (2010) New insights into the relationship between suture closure and craniofacial dysmorphology in sagittal nonsyndromic craniosynostosis. J Anat 217(2):85–96

    PubMed  Google Scholar 

  48. Heuzé Y, Martinez-Abadias N, Stella JM, Senders CW, Boyadjiev SA, Lo LJ, Richtsmeier JT (2011) Unilateral and bilateral expression of a quantitative trait: asymmetry and symmetry in coronal craniosynostosis. J Exp Zool B Mol Dev Evol 318(2):109–122

    Article  Google Scholar 

  49. Hill C, Martínez-Abadías N, Motch S, Austin J, Wang Y, Jabs E, Richtsmeier J, Aldridge K (2012) Growth of the skull and brain dffer pstnatally in a mouse model for Apert syndrome. Am J Med Genet (in press)

  50. Hobar PC, Masson JA, Wilson R, Zerwekh J (1996) The importance of the dura in craniofacial surgery. Plast Reconstr Surg 98(2):217–225

    Article  PubMed  CAS  Google Scholar 

  51. Holland LZ, Holland ND (2001) Evolution of neural crest and placodes: amphioxus as a model for the ancestral vertebrate? J Anat 199:85–98

    Article  PubMed  CAS  Google Scholar 

  52. Holmes G, Basilico C (2012) Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome. Dev Biol 368(2):283–293

    Article  PubMed  CAS  Google Scholar 

  53. Hu HL, Hilton MJ, Tu XL, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132(1):49–60

    Article  PubMed  CAS  Google Scholar 

  54. Huminiecki L, Goldovsky L, Freilich S, Moustakas A, Ouzounis C, Heldin CH (2009) Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom. BMC Evol Biol 9:28–45

    Article  PubMed  CAS  Google Scholar 

  55. Ibrahimi OA, Chiu E, McCarthy J, Mohammadi M (2004) Understanding the molecular basis of Apert syndrome. Plast Reconstr Surg 115:264–270

    Google Scholar 

  56. Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116(7):1157–1173

    Article  PubMed  CAS  Google Scholar 

  57. Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15(23):3059–3087

    Article  PubMed  CAS  Google Scholar 

  58. Iseki S, Morriss-Kay GM, Eto K (2001) Study of fibroblast growth factor receptor signalling during skull vault development by ex-utero surgery. J Hard Tissue Biol 10:25–29

    CAS  Google Scholar 

  59. Iseki S, Wilkie AO, Heath JK, Ishimaru T, Eto K, Morriss-Kay GM (1997) Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2. Development 124(17):3375–3384

    PubMed  CAS  Google Scholar 

  60. Ishii M, Merrill AE, Chan YS, Gitelman I, Rice DPC, Sucov HM, Maxson RE (2003) Msx2 and Twist cooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault. Development 130(24):6131–6142

    Article  PubMed  CAS  Google Scholar 

  61. Ito Y, Yeo JY, Chytil A, Han J, Bringas P, Nakajima A, Shuler CF, Moses HL, Chai Y (2003) Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects. Development 130(21):5269–5280

    Article  PubMed  CAS  Google Scholar 

  62. Itoh N, Ornitz DM (2004) Evolution of the Fgf and Fgfr gene families. Trends Genet 20(11):563–569

    Article  PubMed  CAS  Google Scholar 

  63. Itoh N, Ornitz DM (2008) Functional evolutionary history of the mouse Fgf gene family. Dev Dyn 237(1):18–27

    Article  PubMed  CAS  Google Scholar 

  64. Jiang X, Iseki S, Maxson RE, Sucov HM, Morriss-Kay GM (2002) Tissue origins and interactions in the mammalian skull vault. Dev Biol 241(1):106–116

    Article  PubMed  CAS  Google Scholar 

  65. Johnson D, Wilkie AO (2011) Craniosynostosis. Eur J Hum Genet 19(4):369–376

    Article  PubMed  CAS  Google Scholar 

  66. Johnson M (2008) Wnt signaling and bone. In: Bilezikian J, Raisz L, Martin T (eds) Principles of bone biology, vol 1. 3rd edn. Elsevier, New York, pp 121–137

  67. Justice C, Yagnik G, Kim Y, Peter I, Jabs EW, Erazo M, Ye X, Shi L, Cunningham ML, Kimonis V, Roscioli T, Wall SA, Wilkie AO, Stoler J, Richtsmeier JT, Heuzé Y, Sanchez-Laura P, Buckley M, Druschel C, Naydenov C, Kim J, Wilson A, Boyadjiev SA (2012) A genome-wide association study identifies susceptibility loci for non-syndromic sagittal craniosynostosis on chromosomes 20 and 7. Nat Genet 44:1360–1364

    Article  PubMed  CAS  Google Scholar 

  68. Kalamarides M, Stemmer-Rachamimov AO, Niwa-Kawakita M, Chareyre F, Taranchon E, Han ZY, Martinelli C, Lusis EA, Hegedus B, Gutmann DH, Giovannini M (2011) Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes. Oncogene 30(20):2333–2344

    Article  PubMed  CAS  Google Scholar 

  69. Karaplis A (2008) Embryonic development of bone and regulation of intramembranous and endochondral bone formation. In: Bilezikian J, Raisz L, Martin T (eds) Principles of bone biology, vol 1. 3rd edn. Academic Press, San Diego, pp 53–84

  70. Kardong K (2012) Vertebrates: comparative anatomy, function, evolution, 6th edn. McGraw-Hill, New York

    Google Scholar 

  71. Karsenty G (2006) Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab 4(5):341–348

    Article  PubMed  CAS  Google Scholar 

  72. Karsenty G, Kronenberg HM, Settembre C (2009) Genetic control of bone formation. Annu Rev Cell Dev Biol 25:629–648

    Article  PubMed  CAS  Google Scholar 

  73. Karsenty G, Wagner EF (2002) Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2(4):389–406

    Article  PubMed  CAS  Google Scholar 

  74. Kawasaki K, Buchanan AV, Weiss KM (2009) Biomineralization in humans: making the hard choices in life. Annu Rev Genet 43:119–142

    Article  PubMed  CAS  Google Scholar 

  75. Kjaer I, Keeling JW, Graem N (1991) The midline craniofacial skeleton in holoprosencephalic fetuses. J Med Genet 28(12):846–855

    Article  PubMed  CAS  Google Scholar 

  76. Kondo S, Miura T (2010) Reaction-diffusion model as a framework for understanding biological pattern formation. Science 329(5999):1616–1620

    Article  PubMed  CAS  Google Scholar 

  77. Koyabu D, Maier W, Sanchez-Villagra M (2012) Paleontological and developmental evidence resolve the homology and dual embryonic origin of a mammalian skull bone, the interparietal. Proc Natl Acad Sci USA 109(35):14075–14080

    Article  PubMed  CAS  Google Scholar 

  78. Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423(6937):332–336

    Article  PubMed  CAS  Google Scholar 

  79. Kumar S, Balczarek KA, Lai ZC (1996) Evolution of the hedgehog gene family. Genetics 142(3):965–972

    PubMed  CAS  Google Scholar 

  80. Lana-Elola E, Rice R, Grigoriadis AE, Rice DFC (2007) Cell fate specification during calvarial bone and suture development. Dev Biol 311:335–346

    Google Scholar 

  81. Lander A (2013) How cells know where they are. Science 339(6):923–927

    Article  PubMed  CAS  Google Scholar 

  82. Larsen W (2001) Human embryology, 3rd edn. Mosby, St. Louis

    Google Scholar 

  83. Lathia J, Mattson M, Cheng A (2008) Notch: from neural development to neurological disorders. J Neurochem 107:1471–1481

    Article  PubMed  CAS  Google Scholar 

  84. Le Douarin N, Dupin E (2012) The neural crest in vertebrate evolution. Curr Opin Genet Dev 22:1–19

    Article  CAS  Google Scholar 

  85. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445(7124):168–176

    Article  PubMed  CAS  Google Scholar 

  86. Long FX (2012) Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 13(1):27–38

    Article  CAS  Google Scholar 

  87. Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274(5290):1109–1115

    Article  PubMed  CAS  Google Scholar 

  88. Mao JJ, Nah HD (2004) Growth and development: hereditary and mechanical modulations. Am J Orthod Dentofac Orthop 125(6):676–689

    Article  Google Scholar 

  89. Marcucio RS, Young NM, Hu D, Hallgrimsson B (2011) Mechanisms that underlie co-variation of the brain and face. Genesis 49(4):177–189

    Article  PubMed  Google Scholar 

  90. Marie PJ (2003) Fibroblast growth factor signaling controlling osteoblast differentiation. Gene 316:23–32

    Article  PubMed  CAS  Google Scholar 

  91. Marti E, Bovolenta P (2002) Sonic hedgehog in CNS development: one signal, multiple outputs. Trends Neurosci 25(2):89–96

    Article  PubMed  CAS  Google Scholar 

  92. Martínez-Abadías N, Heuze Y, Wang Y, Jabs EW, Aldridge K, Richtsmeier JT (2011) FGF/FGFR signaling coordinates skull development by modulating magnitude of morphological integration: evidence from Apert syndrome mouse models. PLoS ONE 6(10):e26425

    Article  PubMed  CAS  Google Scholar 

  93. Martinez-Abadias N, Motch SM, Pankratz TL, Wang Y, Aldridge K, Jabs EW, Richtsmeier JT (2013) Tissue-specific responses to aberrant FGF signaling in complex head phenotypes. Dev Dyn 242(1):80–94

    Article  PubMed  CAS  Google Scholar 

  94. Martínez-Abadías N, Percival C, Aldridge K, Hill C, Ryan T, Sirivunnabood S, Wang Y, Jabs E, Richtsmeier JT (2010) Beyond the closed suture in Apert syndrome mouse models: evidence of primary effects of FGFR2 signaling on facial shape at birth. Dev Dyn 239:3058–3071

    Article  PubMed  Google Scholar 

  95. Massagué J (1998) TGF-β signal transduction. Annu Rev Biochem 67:753–791

    Article  PubMed  Google Scholar 

  96. Matus DQ, Magie CR, Pang K, Martindale MQ, Thomsen GH (2008) The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution. Dev Biol 313(2):501–518

    Article  PubMed  CAS  Google Scholar 

  97. Maves L, Jackman W, Kimmel CB (2002) FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain. Development 129(16):3825–3837

    PubMed  CAS  Google Scholar 

  98. McBratney-Owen B, Iseki S, Bamforth SD, Olsen BR, Morriss-Kay GM (2008) Development and tissue origins of the mammalian cranial base. Dev Biol 322(1):121–132

    Article  PubMed  CAS  Google Scholar 

  99. Mizutani CM, Bier E (2008) EvoD/Vo: the origins of BMP signalling in the neuroectoderm. Nat Rev Genet 9(9):663–677

    Article  PubMed  CAS  Google Scholar 

  100. Monteiro A, Podlaha O (2009) Wings, horns, and butterfly eyespots: how do complex traits evolve? PLoS Biol 7(2):02090216

    Article  CAS  Google Scholar 

  101. Morriss-Kay GM (2001) Derivation of the mammalian skull vault. J Anat 199:143–151

    Article  PubMed  CAS  Google Scholar 

  102. Morriss-Kay GM, Wilkie AO (2005) Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies. J Anat 207(5):637–653

    Article  PubMed  Google Scholar 

  103. Moses HL, Serra R (1996) Regulation of differentiation by TGF-beta. Curr Opin Genet Dev 6(5):581–586

    Article  PubMed  CAS  Google Scholar 

  104. Moss M (1962) The functional matrix. In: Kraus B, Reidel R (eds) Vistas in orthodontics. Lea and Febiger, Philadelphia, pp 85–98

    Google Scholar 

  105. Moss M, Young R (1960) A functional approach to craniology. Am J Phys Anthropol 18:281–292

    Article  PubMed  CAS  Google Scholar 

  106. Most D, Levine JP, Chang J, Sung J, McCarthy JG, Schendel SA, Longaker MT (1998) Studies in cranial suture biology: up-regulation of transforming growth factor-beta1 and basic fibroblast growth factor mRNA correlates with posterior frontal cranial suture fusion in the rat. Plast Reconstr Surg 101(6):1431–1440

    Article  PubMed  CAS  Google Scholar 

  107. Muller F, Orahilly R (1991) Development of anencephaly and its variants. Am J Anat 190(3):193–218

    Article  PubMed  CAS  Google Scholar 

  108. Nagata M, Nuckolls GH, Wang X, Shum L, Seki Y, Kawase T, Takahashi K, Nonaka K, Takahashi I, Noman AA, Suzuki K, Slavkin HC (2011) The primary site of the acrocephalic feature in Apert syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling. Bone 48(4):847–856

    Article  PubMed  CAS  Google Scholar 

  109. Nichols SA, Dirks W, Pearse JS, King N (2006) Early evolution of animal cell signaling and adhesion genes. PNAS 103(33):12451–12456

    Article  PubMed  CAS  Google Scholar 

  110. Niehrs C (2010) On growth and form: a Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes. Development 137(6):845–857

    Article  PubMed  CAS  Google Scholar 

  111. Nikitina NV, Bronner-Fraser M (2009) Gene regulatory networks that control the specification of neural-crest cells in the lamprey. BBA Gene Regul Mech 1789(4):274–278

    CAS  Google Scholar 

  112. Noden DM, Trainor PA (2005) Relations and interactions between cranial mesoderm and neural crest populations. J Anat 207(5):575–601

    Article  PubMed  Google Scholar 

  113. Northcutt RG (2005) The new head hypothesis revisited. J Exp Zool Part B 304B(4):274–297

    Article  Google Scholar 

  114. Olsen SK, Ibrahimi OA, Raucci A, Zhang FM, Eliseenkova AV, Yayon A, Basilico C, Linhardt RJ, Schlessinger J, Mohammadi M (2004) Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity. PNAS 101(4):935–940

    Article  PubMed  CAS  Google Scholar 

  115. Opperman LA (2000) Cranial sutures as intramembranous bone growth sites. Dev Dyn 219(4):472–485

    Article  PubMed  CAS  Google Scholar 

  116. Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2(3):1–12

    Article  Google Scholar 

  117. Ornitz DM, Marie PJ (2002) FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev 16(12):1446–1465

    Article  PubMed  CAS  Google Scholar 

  118. Ozawa H, Hoshi K, Amizuka N (2008) Current concepts of bone biomineralization. J Oral Biosci 50:1–14

    Article  Google Scholar 

  119. Panchal J, Marsh JL, Park TS, Kaufman B, Pilgram T, Huang SH (1999) Sagittal craniosynostosis outcome assessment for two methods and timings of intervention. Plast Reconstr Surg 103(6):1574–1584

    PubMed  CAS  Google Scholar 

  120. Passos-Bueno MR, Serti Eacute AE, Jehee FS, Fanganiello R, Yeh E (2008) Genetics of craniosynostosis: genes, syndromes, mutations and genotype-phenotype correlations. Front Oral Biol 12:107–143

    Article  PubMed  Google Scholar 

  121. Patapoutian A, Reichardt L (2000) Roles of Wnt proteins in neural development and maintenance. Curr Biol 10:392–399

    CAS  Google Scholar 

  122. Percival C, Wang Y, Zhou X, Jabs E, Richtsmeier J (2012) The effect of a Beare–Stevenson syndrome Fgfr2 Y394C mutation on early craniofacial bone volume and relative bone mineral density in mice. J Anat 221(5):434–442

    Article  PubMed  Google Scholar 

  123. Plopper GE, Mcnamee HP, Dike LE, Bojanowski K, Ingber DE (1995) Convergence of integrin and growth-factor receptor signaling pathways within the focal adhesion complex. Mol Biol Cell 6(10):1349–1365

    PubMed  CAS  Google Scholar 

  124. Popovici C, Roubin R, Coulier F, Birnbaum D (2005) An evolutionary history of the FGF superfamily. Bioessays 27(8):849–857

    Article  PubMed  CAS  Google Scholar 

  125. Richtsmeier JT, Aldridge K, DeLeon VB, Panchal J, Kane AA, Marsh JL, Yan P, Cole TM (2006) Phenotypic integration of neurocranium and brain. J Exp Zool Part B 306B(4):360–378

    Article  Google Scholar 

  126. Richtsmeier JT, Deleon VB (2009) Morphological integration of the skull in craniofacial anomalies. Orthod Craniofac Res 12(3):149–158. doi:10.1111/j.1601-6343.2009.01448.x

    Article  PubMed  CAS  Google Scholar 

  127. Rochefort GY, Pallu S, Benhamou CL (2010) Osteocyte: the unrecognized side of bone tissue. Osteoporos Int 21(9):1457–1469

    Article  PubMed  CAS  Google Scholar 

  128. Rubenstein JLR, Shimamura K, Martinez S, Puelles L (1998) Regionalization of the prosencephalic neural plate. Annu Rev Neurosci 21:445–477

    Article  PubMed  CAS  Google Scholar 

  129. Sasai Y, DeRobertis EM (1997) Ectodermal patterning in vertebrate embryos. Dev Biol 182(1):5–20

    Article  PubMed  CAS  Google Scholar 

  130. Schinke T, Karsenty G (2008) Transcriptional control of osteoblast differentiation and function. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of bone biology, vol 1. 3rd edn. Academic Press, San Diego, pp 109–111

  131. Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103(2):211–225

    Article  PubMed  CAS  Google Scholar 

  132. Sidoti EJ, Marsh JL, MartyGrames L, Noetzel MJ (1996) Long-term studies of metopic synostosis: frequency of cognitive impairment and behavioral disturbances. Plast Reconstr Surg 97(2):276–281

    Article  PubMed  Google Scholar 

  133. Sloan GM, Wells KC, Raffel C, McComb JG (1997) Treatment of craniosynostosis: outcome analysis of 250 consecutive patients. Pediatrics 100(1):e2

    Google Scholar 

  134. Sperber G, Sperber S, Guttmann G (2010) Craniofacial embryogenetics and development. People’s Medical Publishing House, Shelton

  135. Streit A (2008) The cranial sensory nervous system: specification of sensory progenitors and placodes. In: StemBook. Harvard Stem Cell Institute, Cambridge

  136. Striedter G (2004) Principles of brain evolution. Sinauer Associates

  137. Sylvester JB, Rich CA, Loh YHE, van Staaden MJ, Fraser GJ, Streelman JT (2010) Brain diversity evolves via differences in patterning. PNAS 107(21):9718–9723

    Article  PubMed  CAS  Google Scholar 

  138. Temiyasathit S, Jacobs CR (2010) Osteocyte primary cilium and its role in bone mechanotransduction. Ann N Y Acad Sci 1192:422–428

    Article  PubMed  CAS  Google Scholar 

  139. Theodosiou A, Arhondakis S, Baumann M, Kossida S (2009) Evolutionary scenarios of notch proteins. Mol Biol Evol 26(7):1631–1640

    Article  PubMed  CAS  Google Scholar 

  140. Thisse B, Thisse C (2005) Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol 287(2):390–402

    Article  PubMed  CAS  Google Scholar 

  141. Ting MC, Wu NL, Roybal PG, Sun J, Liu L, Yen Y, Maxson RE Jr (2009) EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development 136(5):855–864

    Article  PubMed  CAS  Google Scholar 

  142. Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10(2):116–129

    Article  PubMed  CAS  Google Scholar 

  143. Vivatbutsiri P, Ichinose S, Hytonen M, Sainio K, Eto K, Iseki S (2008) Impaired meningeal development in association with apical expansion of calvarial bone osteogenesis in the Foxc1 mutant. J Anat 212(5):603–611

    Article  PubMed  CAS  Google Scholar 

  144. Volpe P, Campobasso G, De Robertis V, Rembouskos G (2009) Disorders of prosencephalic development. Prenat Diagn 29(4):340–354

    Article  PubMed  CAS  Google Scholar 

  145. Wada H, Satoh N (2001) Patterning the protochordate neural tube. Curr Opin Neurobiol 11(1):16–21

    Article  PubMed  CAS  Google Scholar 

  146. Wang Y, Sun M, Uhlhorn VL, Zhou X, Peter I, Martinez-Abadias N, Hill CA, Percival CJ, Richtsmeier JT, Huso DL, Jabs EW (2010) Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2(+P253R) mice. BMC Dev Biol 10:22

    Article  PubMed  CAS  Google Scholar 

  147. 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 (2005) Abnormalities in cartilage and bone development in the Apert syndrome FGFR2(+/S252W) mouse. Development 132(15):3537–3548

    Article  PubMed  CAS  Google Scholar 

  148. Wang YL, Zhou XY, Oberoi K, Phelps R, Couwenhoven R, Sun M, Rezza A, Holmes G, Percival CJ, Friedenthal J, Krejci P, Richtsmeier JT, Huso DL, Rendl M, Jabs EW (2012) p38 inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare–Stevenson mice. J Clin Invest 122(6):2153–2164

    Article  PubMed  CAS  Google Scholar 

  149. Weiss KM, Buchanan A, Richtsmeier J, Cheverud J, Rogers J, Ryan T, Gillespie L, Lawson H, Zhang J, Cannon N, Percival C (2013) Getting ahead: genetic aspects of craniofacial variation as reflected in a mouse model (in preparation)

  150. Wilkie AO, Byren JC, Hurst JA, Jayamohan J, Johnson D, Knight SJ, Lester T, Richards PG, Twigg SR, Wall SA (2010) Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis. Pediatrics 126(2):e391–e400

    Article  PubMed  Google Scholar 

  151. Wilkie AO, Morriss-Kay GM (2001) Genetics of craniofacial development and malformation. Nat Rev Genet 2(6):458–468

    Article  PubMed  CAS  Google Scholar 

  152. Worthington JJ, Klementowicz JE, Travis MA (2011) TGF beta: a sleeping giant awoken by integrins. Trends Biochem Sci 36(1):47–54

    Article  PubMed  CAS  Google Scholar 

  153. Wurst W, Bally-Cuif L (2001) Neural plate patterning: upstream and downstream of the isthmic organizer. Nat Rev Neurosci 2(2):99–108

    Article  PubMed  CAS  Google Scholar 

  154. Yen HY, Ting MC, Maxson RE (2010) Jagged1 functions downstream of Twist1 in the specification of the coronal suture and the formation of a boundary between osteogenic and non-osteogenic cells. Dev Biol 347(2):258–270

    Article  PubMed  CAS  Google Scholar 

  155. Yoshida T, Phylactou LA, Uney JB, Ishikawa I, Eto K, Iseki S (2005) Twist is required for establishment of the mouse coronal suture. J Anat 206(5):437–444

    Article  PubMed  CAS  Google Scholar 

  156. Yu JC, Lucas JH, Fryberg K, Borke JL (2001) Extrinsic tension results in FGF-2 release, membrane permeability change, and intracellular Ca++ increase in immature cranial sutures. J Craniofac Surg 12(4):391–398

    Article  PubMed  CAS  Google Scholar 

  157. Zumpano M, Carson B, Marsh J, Vanderkolk C, Richtsmeier J (1999) Three-dimensional morphological analysis of isolated metopic synostosis. Anat Rec 256(2):177–188

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors take full responsibility for ideas and data presented in this manuscript. JTR thanks Drs. Kristina Aldridge and Ethylin Wang Jabs for discussions about craniosynostosis over the years that helped mold her view about these conditions. We thank Dr. Anne Buchanan for a critical evaluation of a previous version of this paper and two anonymous reviewers whose comments helped to shape the final version. Drs. Susan Motch and Christopher Percival were instrumental in compiling information and data for Figs. 2 and 8. Human CT data from our image archive are maintained according to approved IRB protocols of the Pennsylvania State University. The work presented in this paper was supported in part by NIDCR/NIH R01DE018500, R01DE022988; NIDCR/NIH and ARRA 3R01DE018500-02S1; NSF BCS 0725227.

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The authors declare that they have no conflict of interest.

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  1. Department of Anthropology, Pennsylvania State University, 409 Carpenter Building, University Park, Pennsylvania, 16802, USA

    Joan T. Richtsmeier & Kevin Flaherty

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Richtsmeier, J.T., Flaherty, K. Hand in glove: brain and skull in development and dysmorphogenesis. Acta Neuropathol 125, 469–489 (2013). https://doi.org/10.1007/s00401-013-1104-y

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