title: Foxc1 integrates Fgf and Bmp signalling independently of twist or noggin during calvarial bone development.
abstract: Calvarial bone and suture development is under complex regulation where bone morphogenetic protein (Bmp) and fibroblast growth factor (Fgf) signalling interact with Msx2/Twist and Noggin and regulate frontal bone primordia proliferation and suture fusion, respectively. We have shown previously that the winged helix transcription factor Foxc1, which is necessary for calvarial bone development, is required for the Bmp regulation of Msx2. We now show that FGF2 regulates the expression of Foxc1, indicating that Foxc1 integrates Bmp and Fgf signalling pathways. We also show that Foxc1 is not needed for the acquisition of osteogenic potential or for the differentiation of osteoblasts. The expression of Fgf receptors and Twist were normal in Foxc1-deficient calvarial mesenchyme, and ectopic FGF2 was able to induce the expression Osteopontin. Furthermore, we demonstrate that Foxc1 does not participate in the regulation of Noggin expression. Our findings indicate that Foxc1 integrates the Bmp and Fgf signalling pathways independently of Twist or Noggin. This signalling network is essential for the correct patterning and growth of calvarial bones.
authors.affiliation: Developmental Biology Programme, Institute of Biotechnology, University of Helsinki, Finland. ritva.rice@kcl.ac.uk
authors.forename: Ritva
authors.initials: R
authors.lastname: Rice
authors.forename: David P C
authors.initials: DP
authors.lastname: Rice
authors.forename: Irma
authors.initials: I
authors.lastname: Thesleff
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D016222:Fibroblast Growth Factor 2; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D000099176:Noggin Protein; C112890:Foxc1 protein, mouse; C103173:TWIST1 protein, human