1Department of Anthropology, Penn State University, 2Department of Biomedical Engineering, Wash U in St Louis, 3Department of Genetics and Genomic Genomic Sciences, Mt Sinai School of Medicine
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The bases of craniofacial skeletal size and shape variation within modern populations and across evolutionary history is extremely complex. A large number of genetic factors and epigenetic interactions guide the development of craniofacial bones. Given the critical role that blood vessel growth (angiogenesis) plays during skeletogenesis, we hypothesize that modification of angiogenic processes can produce novel evolutionarily relevant variation in calvarial bone morphology during fetal vault skeletogenesis.
The Fgfr2+/P253R Apert syndrome mouse model with known craniofacial dysmorphology was studied because fibroblast growth factor (Fgf) and receptor (Fgfr) interactions are known to influence angiogenesis. Additionally, significant reductions in craniofacial bone size and bone density are associated with conditional Tek-cre based expression of the Fgfr2 +/P253R mutation in vascular endothelial cells. Simultaneous Optical Coherence Tomography and Photoacoustic Microscopy (OCT/PAM) produced 3D images of blood vessels and tissue layers surrounding the developing left frontal bone of Fgfr2+/P253R mutant mice and littermates at embryonic days 13.5, 14.5, 15.5, and 16.5. For some specimens, bones identified using micro-computed tomography (μCT) were registered to OCT/PAM images. Careful comparison revealed no clear differences in vascular patterns associated with early frontal bone skeletogenesis between mutant mice and unaffected littermates. Therefore, fetal modification of vascular patterns may not be the basis of previously measured abnormal calvarial bone dimensions associated with expression of this mutation in vascular endothelium. Further studies are required to explore other potential regulatory connections between angiogenesis and evolutionarily relevant craniofacial skeletal variation.
This work was supported by grants from the NSF(BCS-1061554) and NIH/NIDCR (R01DE18500; R01DE18500-S2).