Abstract
BackgroundAs a culmination of efforts over the last years, our knowledge of the embryonic origins of the mammalian frontal and parietal cranial bones is unambiguous. Progenitor cells that subsequently give rise to frontal bone are of neural crest origin, while parietal bone progenitors arise from paraxial mesoderm. Given the unique qualities of neural crest cells and the clear delineation of the embryonic origins of the calvarial bones, we sought to determine whether mouse neural crest derived frontal bone differs in biology from mesoderm derived parietal bone.MethodsBrdU incorporation, immunoblotting and osteogenic differentiation assays were performed to investigate the proliferative rate and osteogenic potential of embryonic and postnatal osteoblasts derived from mouse frontal and parietal bones. Co-culture experiments and treatment with conditioned medium harvested from both types of osteoblasts were performed to investigate potential interactions between the two different tissue origin osteoblasts. Immunoblotting techniques were used to investigate the endogenous level of FGF-2 and the activation of three major FGF signaling pathways. Knockdown of FGF Receptor 1 (FgfR1) was employed to inactivate the FGF signaling.ResultsOur results demonstrated that striking differences in cell proliferation and osteogenic differentiation between the frontal and parietal bone can be detected already at embryonic stages. The greater proliferation rate, as well as osteogenic capacity of frontal bone derived osteoblasts, were paralleled by an elevated level of FGF-2 protein synthesis. Moreover, an enhanced activation of FGF-signaling pathways was observed in frontal bone derived osteoblasts. Finally, the greater osteogenic potential of frontal derived osteoblasts was dramatically impaired by knocking down FgfR1.ConclusionsOsteoblasts from mouse neural crest derived frontal bone displayed a greater proliferative and osteogenic potential and endogenous enhanced activation of FGF signaling compared to osteoblasts from mesoderm derived parietal bone. FGF signaling plays a key role in determining biological differences between the two types of osteoblasts.
Highlights
Bones of the cranial vault form through the process of intramembranous ossification [1]
These studies have defined the pattern of cranial neural crest cell migration in mouse embryos and demonstrated that the frontal bone is of neural crest origin, whereas the parietal bone is of mesoderm origin
Our recent study demonstrated that frontal bones of both juvenile and adult mice are endowed with superior regenerative potential compared to parietal bones, and osteoblasts derived from either juvenile or adult frontal bone display increased potential for proliferation and osteogenic differentiation when compared to osteoblasts obtained from the parietal bone [27]
Summary
Bones of the cranial vault form through the process of intramembranous ossification [1]. Calvarial bones arise from two embryonic tissue origins, namely the neural crest and mesoderm. The distinct contributions of each tissue to the skull have been well established by combining mice with a Wnt1-Cre construct and a conditional reporter gene, R26R [2,3]. These studies have defined the pattern of cranial neural crest cell migration in mouse embryos and demonstrated that the frontal bone is of neural crest origin, whereas the parietal bone is of mesoderm origin. Given the unique qualities of neural crest cells and the clear delineation of the embryonic origins of the calvarial bones, we sought to determine whether mouse neural crest derived frontal bone differs in biology from mesoderm derived parietal bone
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