Conserved molecular program regulating cranial and appendicular skeletogenesis.

Abstract

The majority of in vivo studies on bone and cartilage differentiation are carried out using the appendicular skeleton as a model system, with the implicit assumption that skeletal formation is equivalent throughout the body. This assumption persists, despite differences in the cellular origins of the skeletogenic precursors. To test the hypothesis that a fundamental set of genes directs skeletal cell differentiation throughout the body, we analyzed cartilage and bone of the chick limb and head during mesenchymal condensation, and when the skeletal tissues had matured. First, we analyzed the expression patterns of transcription factors in early skeletogenic condensations, which revealed similarities among skeletal cell specification in the limb and head. For example, skeletogenic condensations that undergo endochondral ossification had equivalent expression patterns of skeletogenic transcription factors in both limb and head. In the head, many elements also differentiate through intramembranous ossification, or through persistent cartilage formation. Our analyses of these skeletogenic condensations revealed that a unique expression pattern of transcription factors distinguishes among three skeletal tissue fates. The vasculature was excluded from all three skeletogenic condensations, demonstrating that this is not a characteristic unique to endochondral ossification. Second, we compared three different types of more mature cartilage and bone tissue in both the limb and the head, by analyzing a variety of skeletal collagens and signaling molecules. Histological and molecular markers of cartilage and bone generally were conserved between the limb and head skeletons, although we uncovered subtle differences in signaling pathways that might influence cranial and appendicular skeletogenesis.