Come together over me: Cells that form the dermatocranium and chondrocranium in mice

Abstract

Most bone develops either by intramembranous ossification where bone forms within a soft connective tissue, or by endochondral ossification by way of a cartilage anlagen or model. Bones of the skull can form endochondrally or intramembranously or represent a combination of the two types of ossification. Contrary to the classical definition of intramembranous ossification, we have previously described a tight temporo‐spatial relationship between cranial cartilages and dermal bone formation and proposed a mechanistic relationship between chondrocranial cartilage and dermal bone. Here, we further investigate this relationship through an analysis of how cells organize to form cranial cartilages and dermal bone. Using Wnt1‐Cre2 and Mesp1‐Cre transgenic mice, we determine the derivation of cells that comprise cranial cartilages from either cranial neural crest (CNC) or paraxial mesoderm (PM). We confirm a previously determined CNC‐PM boundary that runs through the hypophyseal fenestra in the cartilaginous braincase floor and identify four additional CNC‐PM boundaries in the chondrocranial lateral wall, including a boundary that runs along the basal and apical ends of the hypochiasmatic cartilage. Based on the knowledge that as osteoblasts differentiate from CNC‐ and PM‐derived mesenchyme, the differentiating cells express the transcription factor genes RUNX2 and osterix (OSX), we created a new transgenic mouse line called R2Tom. R2Tom mice carry a tdTomato reporter gene joined with an evolutionarily well‐conserved enhancer sequence of RUNX2. R2Tom mice crossed with Osx‐GFP mice yield R2Tom;Osx‐GFP double transgenic mice in which various stages of osteoblasts and their precursors are detected with different fluorescent reporters. We use the R2Tom;Osx‐GFP mice, new data on the cell derivation of cranial cartilages, histology, immunohistochemistry, and detailed morphological observations combined with data from other investigators to summarize the differentiation of cranial mesenchyme as it forms condensations that become chondrocranial cartilages and associated dermal bones of the lateral cranial wall. These data advance our previous findings of a tendency of cranial cartilage and dermal bone development to vary jointly in a coordinated manner, promoting a role for cranial cartilages in intramembranous bone formation.

Allometry of Human Calvaria Bones During Development From Birth to 8 Years of Age

“…A total of 177 images were included in the BP sample. From the BCCH sample, 221 images were selected initially, and thirteen (13) images were excluded during the second review due to images missing the cranial base (7), movement artifacts (1), bone fracture (1), or images showing only the cranial base (4). A total of 187 images were included from the Canadian sample.…”

“…The ossification of the skull bones starts at 5 to 6 weeks of gestation and occurs both intramembranously and endochondrally. (3,4) The junction of the osteogenic fronts was sutured by 16 weeks (approximately 3 and a half months) of gestation. (5,6) The continuous development of the child's calvaria creates significant differences in skull sizes and patterns between infants and young children of different ages.…”