FGF9 can induce endochondral ossification in cranial mesenchyme.
BACKGROUND
The flat bones of the skull (i.e., the frontal and parietal bones) normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone.


RESULTS
We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF), in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm.


CONCLUSIONS
These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of) mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification.
Govindarajan
Venkatesh
V
Cancer Center, Creighton University, Omaha, NE 68178, USA. g.v@creighton.edu
Overbeek
Paul A
PA
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D051525:Fibroblast Growth Factor 9 / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D010012:Osteogenesis; D010294:Parietal Bone / Q000166:cytology / Q000196:embryology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D012886:Skull / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development
D015415:Biomarkers; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; C496366:Fgfr3 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3