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Fgfr1 conditional-knockout in neural crest cells induces heterotopic chondrogenesis and osteogenesis in mouse frontal bones

  • Mariko Kawai
  • David Herrmann
  • Alisa Fuchs
  • Shuofei Cheng
  • Anna Ferrer-Vaquer
  • Rebekka Götz
  • Katrin Driller
  • Annette Neubüser
  • Kiyoshi Ohura
Original Paper
  • 65 Downloads

Abstract

Most facial bones, including frontal bones, are derived from neural crest cells through intramembranous ossification. Fibroblast growth factor receptor 1 (Fgfr1) plays a pivotal role in craniofacial bone development, and loss of Fgfr1 leads to cleft palate and facial cleft defects in newborn mice. However, the potential role of the Fgfr1 gene in neural crest cell-mediated craniofacial development remains unclear. To investigate the role of Fgfr1 in neural crest cells, we analyzed Wnt1-Cre;Fgfr1flox/flox mice. Our results show that specific knockout of Fgfr1 in neural crest cells induced heterotopic chondrogenesis and osteogenesis at the interface of the anterior portions of frontal bones. We observed that heterotopic bone formation continued through postnatal day 28, whereas heterotopic chondrogenesis lasted only through the embryonic period. In summary, our results indicate that loss of Fgfr1 in neural crest cells leads to heterotopic chondrogenesis and osteogenesis.

Keywords

Fgfr1 Neural crest cell Frontal bone Chondrogenesis Osteogenesis 

Notes

Acknowledgements

We thank Dr. Wolfgang Driever and his laboratory at Freiburg University. This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Basic Research C Number 24300182) and Nakatomi Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Le Lievre CS (1978) Participation of neural crest-derived cells in the genesis of the skull in birds. J Embryol Exp Morphol 47:17–37PubMedGoogle Scholar
  2. 2.
    Jiang X, Iseki S, Maxson RE, Sucov HM, Morriss-Kay GM (2002) Tissue origins and interactions in the mammalian skull vault. Dev Biol 241:106–116CrossRefGoogle Scholar
  3. 3.
    Moosa S, Wollnik B (2016) Altered FGF signalling in congenital craniofacial and skeletal disorders. Semin Cell Dev Biol 53:115–125CrossRefGoogle Scholar
  4. 4.
    Yamaguchi TP, Harpal K, Henkemeyer M, Rossant J (1994) Fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. Genes Dev 15:3032–3044CrossRefGoogle Scholar
  5. 5.
    Trokovic N, Trokovic R, Mai P, Partanen J (2003) Fgfr1 regulates patterning of the pharyngeal region. Genes Dev 17:141–153CrossRefGoogle Scholar
  6. 6.
    Trokovic R, Trokovic N, Hernesniemi S, Pirvola U, Weisenhorn DM, Rossant J, McMahon AP, Wurst W, Partanen J (2003) FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals. EMBO J 22:1811–1823CrossRefGoogle Scholar
  7. 7.
    Danielian PS, Muccino D, Rowitch DH, Michael SH, McMahon AP (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol 8:1323–1326CrossRefGoogle Scholar
  8. 8.
    Adams JC (1992) Biotin amplification of biotin and horseradish peroxidase signals in histochemical stains. J Histochem Cytochem 40:1457–1463CrossRefGoogle Scholar
  9. 9.
    Shibata S, Fujimori T, Yamashita Y (2006) An in situ hybridization and histochemical study of development and postnatal changes of mouse mandibular angular cartilage compared with condylar cartilage. J Med Dent Sci 53:41–50PubMedGoogle Scholar
  10. 10.
    Yamamoto H, Ito K, Kawai M, Murakami Y, Bessho K, Ito Y (2006) RunX3 expression during mouse tongue and palate development. Anat Rec A Discov Mol Cell Evol Biol 288:695–699CrossRefGoogle Scholar
  11. 11.
    Okubo Y, Bessho K, Fujimura K, Iizuka T, Miyatake S (1999) Osteoinduction by bone morphogenetic protein-2 via adenoviral vector in C2C12 myoblasts induces differentiation in to the osteoblast lineage. Biochem Biophys Res Commun 267:382–387CrossRefGoogle Scholar
  12. 12.
    Connery HV, Briggs AR (1966) Determination of serum calcium by means of orthocresolphthalein complex one. Am J Clin Pathol 45:290–296CrossRefGoogle Scholar
  13. 13.
    Naiche LA, Papaioannou VE (2007) Cre activity causes widespread apoptosis and lethal anemia during embryonic development. Genesis 45:768–775CrossRefGoogle Scholar
  14. 14.
    Kobayashi T, Kronenberg HM (2014) Overview of skeletal development. Methods Mol Biol 1130:3–12CrossRefGoogle Scholar
  15. 15.
    Parada C, Chai Y (2015) Mandible and tongue development. Curr Top Dev Biol 115:31–58CrossRefGoogle Scholar
  16. 16.
    Chai Y, Jiang X, Ito Y, Bringas PJ, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679PubMedGoogle Scholar
  17. 17.
    Sakakura Y, Tsuruga E, Irie K, Hosokawa Y, Nakamura H, Yajima T (2005) Immunolocalization of receptor activator of nuclear factor-kappaB ligand (RANKL)and osteoprotegerin (OPG) in Meckel’s cartilage compared with developing endochondral bones in mice. J Anat 207:325–337CrossRefGoogle Scholar
  18. 18.
    Sakakura Y, Hosokawa Y, Tsuruga E, Irie K, Yajima T (2007) In situ localization of gelatinolytic activity during development and resorption of Mechel’s cartilage in mice. Eur J Oral Sci 115:212–223CrossRefGoogle Scholar
  19. 19.
    Roybal PG, Wu NL, Sun J, Ting MC, Schafer CA, Maxson RE (2010) Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head. Dev Biol 34:328–339Google Scholar
  20. 20.
    Maruyama T, Mirando AJ, Deng CX, Hsu W (2010) The balance of WNT and FGF signaling influences mesenchymal stem cell fate during skeletal development. Sci Signal 3(123):ra40.  https://doi.org/10.1126/scisignal.2000727 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kim HJ, Rice DP, Kethunen PJ, Thesleff I (1998) FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development 12587:1241–1251Google Scholar
  22. 22.
    Rice DP, Aberg T, Chan Y, Tang Z, Kettunen PJ, Pakarinen L, Maxson RE, Thesleff I (2000) Integration of FGF and TWIST in calvarial bone and suture development. Development 127:1845–1855PubMedGoogle Scholar
  23. 23.
    Sahar DE, Longaker MT, Quarto N (2005) Sox9 neural crest determinant gene controls patterning and closure of the posterior frontal cranial suture. Dev Biol 280:344–361CrossRefGoogle Scholar
  24. 24.
    Sanches-Lara PA, Graham JMJ, HIng AV, Lee J, Cunningham M (2007) The morphogenesis of wormian bones: a study of craniosynostosis and purposeful cranial deformation. Am J Med Genet A 143:3243–3251CrossRefGoogle Scholar
  25. 25.
    Marti B, Sininelli D, Maurin L, Carpentier E (2013) Wormian bones in a general peadiatric population. Diagn Interv Imaging 94:428–432CrossRefGoogle Scholar
  26. 26.
    Bellary SS, Steinberg A, Mirzayan N, Shiral M, Tubbs RS, Cohen-Gadol AA, Loukas M (2013) Wormian bones: a review. Clin Anat 26:922–927CrossRefGoogle Scholar
  27. 27.
    Semler O, Cheung MS, Glorieux FH, Rauch F (2010) Wormian bones in osteogenesis imperfecta: correlation to clinical findings and genetype. Am J Med Genet A152:1681–1688CrossRefGoogle Scholar

Copyright information

© The Japanese Society for Clinical Molecular Morphology 2018

Authors and Affiliations

  • Mariko Kawai
    • 1
    • 2
  • David Herrmann
    • 2
  • Alisa Fuchs
    • 2
  • Shuofei Cheng
    • 2
  • Anna Ferrer-Vaquer
    • 2
  • Rebekka Götz
    • 2
  • Katrin Driller
    • 2
  • Annette Neubüser
    • 2
  • Kiyoshi Ohura
    • 1
  1. 1.Department of PharmacologyOsaka Dental UniversityHirakataJapan
  2. 2.Department of Developmental Biology, Institute of Biology IUniversity of FreiburgFreiburgGermany

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