Abstract
BackgroundThe 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.ResultsWe 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.ConclusionThese 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.
Highlights
The flat bones of the skull normally form through intramembranous ossification
Bone development can occur in two distinct ways: 1) through endochondral ossification where the mesenchymal cells differentiate into chondrocytes and lay down a cartilaginous template that is later replaced by bone; or 2) through intramembranous ossification where mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate
Changes in cranial morphology in the FGF9 transgenic mice Transgenic mice were generated by microinjection of a construct with the αA-crystallin promoter linked to a mouse Fgf9 cDNA (Fig. 1A) [29]
Summary
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. Cranial mesenchymal cells directly differentiate into osteoblasts that initiate mineralization and secrete an extracellular matrix rich in Collagen I [3]. Growth of these calvarial bones occurs through proliferation and differentiation of (page number not for citation purposes)
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