The chondrocranium in craniofacial development and disease

The dermatocranium that comprises the dermal bones of the cranial vault and facial skeleton is the second cranial skeleton to form during embryogenesis. The chondrocranium, a completely separate cranial skeleton formed of cartilage, develops earlier to support the embryonic brain and other sense organs. Though parts of the chondrocranium ossify endochondrally, other portions begin to degenerate by about embryonic day 15-16 in the mouse. We present preliminary support of our central hypothesis: that the chondrocranium serves as a structural and functional scaffold for the later development of dermatocranial elements including the formation of cranial vault sutures. Since the chondrocranium includes irregularly shaped, short-lived cartilages, its analysis requires new tools for staging embryos and for visualization of embryonic cartilage in 3D. We use in silico reconstructions of the chondrocranium from micro computed tomography images to precisely delineate chondrocranial anatomy in 3D over embryonic time to establish its role in development of the dermatocranium. Based on the common finding that boundaries between different cell populations often serve as tissue organizers, we interrogate the chondrocranial/dermatocranial boundary as significant to the coordinated development of the skull. We examine this boundary in Fgfr2c+/C342Y Crouzon mice and unaffected littermates focusing particularly on how the chondrocranial/dermatocranial boundary might contribute to two craniosynostosis phenotypes: premature closure of the coronal suture and abnormal growth of the midface.