Abstract
Although endochondral ossification of the limb and axial skeleton is relatively well-understood, the development of dermal (intramembranous) bone featured by many craniofacial skeletal elements is not nearly as well-characterized. We analyzed the expression domains of a number of markers that have previously been associated with endochondral skeleton development to define the cellular transitions involved in the dermal ossification process in both chick and mouse. This led to the recognition of a series of distinct steps in the dermal differentiation pathways, including a unique cell type characterized by the expression of both osteogenic and chondrogenic markers. Several signaling molecules previously implicated in endochondrial development were found to be expressed during specific stages of dermal bone formation. Three of these were studied functionally using retroviral misexpression. We found that activity of bone morphogenic proteins (BMPs) is required for neural crest-derived mesenchyme to commit to the osteogenic pathway and that both Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP, PTHLH) negatively regulate the transition from preosteoblastic progenitors to osteoblasts. These results provide a framework for understanding dermal bone development with an aim of bringing it closer to the molecular and cellular resolution available for the endochondral bone development.
Highlights
Mineralized skeleton provides the structural framework underlying the morphology of the head and trunk in most modern vertebrates
Expression of molecular markers during the development of dermal bone To identify the cellular transitions in the development of dermal bone, we analyzed the expression of a number of chondrogenic and osteogenic markers in chick and mouse embryos
Pre-skeletal, alkaline phosphatase-positive, mesenchymal condensations can be detected at stage HH30 [Hamburger-Hamilton stage 30 or embryonic day 7 (E7)]; mineralized bone matrix deposition in the skull begins at around HH36 (E10); osteogenesis is well underway at HH39 (E13) and most of the skeletal structures are in place by HH41 (E15) (Fig. 1B) (Hamburger and Hamilton, 1951; Hall and Miyake, 1992; Dunlop and Hall, 1995; Eames and Helms, 2004)
Summary
Mineralized skeleton provides the structural framework underlying the morphology of the head and trunk in most modern vertebrates. These skeletal elements arise in two developmentally distinct ways. Many of the bones of the craniofacial skeleton arise directly from cranial dermis via a process termed intramembranous bone formation (Fig. 1A) (Noden, 1983; Noden, 1991; Hall and Miyake, 1992; Dunlop and Hall, 1995; Jiang et al, 2002) (reviewed in Helms and Schneider, 2003). Intramembranous bones are classified into three categories: the sesamoid bones, which form in tendons as a result of mechanical stress (such as the patella in the tendon of the quadriceps femoris); the periosteal bones, which form from connective tissue and add to the thickness of long bones; and the dermal bones, which form within the dermis of the skin
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