Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures

Michael A. Ignelzi, Wei Wang, Andrew Young

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Craniosynostosis, the premature fusion of the skull bones at the sutures, represents a disruption to the coordinated growth and development of the expanding brain and calvarial vault and is the second most common birth defect that affects the craniofacial complex. Mutations in the human homeobox-containing gene, Msx2, have been shown to cause Boston type craniosynostosis, and we have shown that overexpression of Msx2 leads to craniosynostosis in mice. Activating mutations in fibroblast growth factor (FGF) receptors are thought to cause craniosynostosis in Crouzon, Apert, Jackson-Weiss, Beare-Stevenson, and Muenke syndromes. To mimic activated signaling by mutated FGF receptors, we used heparin acrylic beads to deliver FGF ligands to mouse calvaria and demonstrated increased Msx2, Runx2, Bsp, and Osteocalcin gene expression, decreased cell proliferation, and suture obliteration and fusion. FGF2 elicited the greatest increase in Msx2 expression, and FGF1 was most likely to cause suture obliteration and fusion. Of the three sutures studied, the coronal suture exhibited the greatest increase in Msx2 expression and was the most likely to undergo obliteration and fusion. These results are intriguing because the coronal suture is the most commonly affected suture in syndromic craniosynostosis. These results suggest that Msx2 is a downstream target of FGF receptor signaling and that increased FGF signaling leads to osteogenic differentiation by sutural mesenchyme in mouse calvaria. These results are consistent with the hypotheses that increased Msx2 expression and activated signaling by mutated FGF receptors lead to craniosynostosis.

Original languageEnglish (US)
Pages (from-to)751-759
Number of pages9
JournalJournal of Bone and Mineral Research
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Fingerprint

Fibroblast Growth Factors
Sutures
Craniosynostoses
Fibroblast Growth Factor Receptors
Skull
Fibroblast Growth Factor 1
Mutation
Homeobox Genes
Osteocalcin
Fibroblast Growth Factor 2
Mesoderm
Growth and Development
Heparin
Cell Proliferation
Ligands
Gene Expression
Bone and Bones
Brain

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. / Ignelzi, Michael A.; Wang, Wei; Young, Andrew.

In: Journal of Bone and Mineral Research, Vol. 18, No. 4, 01.04.2003, p. 751-759.

Research output: Contribution to journalArticle

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