3D-Cephalometric Analysis based on afferent sense

The new benchmarks to determine the human skull precisely in 3D for the investigation of anatomic symmetry and asymmetry to verify the sagittal midline plane reference.

Shaping modern human skull through epigenetic, transcriptional and post-transcriptional regulation of the RUNX2 master bone gene

RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, and playing a specific role in craniofacial and skull morphogenesis. The anatomically modern human (AMH) features sequence changes in the RUNX2 locus compared with archaic hominins’ species. We aimed to understand how these changes may have contributed to human skull globularization occurred in recent evolution. We compared in silico AMH and archaic hominins’ genomes, and used mesenchymal stromal cells isolated from skull sutures of craniosynostosis patients for in vitro functional assays. We detected 459 and 470 nucleotide changes in noncoding regions of the AMH RUNX2 locus, compared with the Neandertal and Denisovan genomes, respectively. Three nucleotide changes in the proximal promoter were predicted to alter the binding of the zinc finger protein Znf263 and long-distance interactions with other cis-regulatory regions. By surface plasmon resonance, we selected nucleotide substitutions in the 3’UTRs able to affect miRNA binding affinity. Specifically, miR-3150a-3p and miR-6785-5p expression inversely correlated with RUNX2 expression during in vitro osteogenic differentiation. The expression of two long non-coding RNAs, AL096865.1 and RUNX2-AS1, within the same locus, was modulated during in vitro osteogenic differentiation and correlated with the expression of specific RUNX2 isoforms. Our data suggest that RUNX2 may have undergone adaptive phenotypic evolution caused by epigenetic and post-transcriptional regulatory mechanisms, which may explain the delayed suture fusion leading to the present-day globular skull shape.

Assessments of bilateral asymmetry with application in human skull analysis

As a common feature, bilateral symmetry of biological forms is ubiquitous, but in fact rarely exact. In a setting of analytic geometry, bilateral symmetry is defined with respect to a point, line or plane, and the well-known notions of fluctuating asymmetry, directional asymmetry and antisymmetry are recast. A meticulous scheme for asymmetry assessments is proposed and explicit solutions to them are derived. An investigation into observational errors of points representing the geometric structure of an object offers a baseline reference for asymmetry assessment of the object. The proposed assessments are applicable to individual, part or all point pairs at both individual and collective levels. The exact relationship between the developed treatments and the widely used Procrustes method in asymmetry assessment is examined. An application of the proposed assessments to a large collection of human skull data in the form of 3D landmark coordinates finds: (a) asymmetry of most skulls is not fluctuating, but directional if measured about a plane fitted to shared landmarks or side landmarks for balancing; (b) asymmetry becomes completely fluctuating if one side of a skull could be slightly rotated and translated with respect to the other side; (c) female skulls are more asymmetric than male skulls. The methodology developed in this study is rigorous and transparent, and lays an analytical base for investigation of structural symmetries and asymmetries in a wide range of biological and medical applications.

The skull

The human skull is the skeleton of the head and is considered along with the mandible. It consists of paired bones and unpaired midline bones that contribute to the muscular attachments for mastication and facial expression, a bony foundation for the upper aerodigestive tract and support and housing for the special sensory organs, brain and other structures susceptible to trauma. The skull without the mandible is termed the cranium and consists of the neurocranium and viscerocranium (facial skeleton). The upper third of the skull is principally formed by the frontal bones and exaggerated at the superciliary ridges of the superior orbit and smooth glabella region centrally. The paired maxillary bones form the middle third, creating the circumference of the piriform aperture between, and are separated from the frontal and temporal bones by the zygoma laterally. They house the maxillary sinuses and meet in the midline inferiorly to form the upper jaw and most of the hard palate at the intermaxillary suture.