Sakib Hussain
Research Mentor: Yuji Mishina
Mentor Department: Biological and Material Sciences, Dentistry
Author(s): Sakib Hussain, Sher Khehra, Mylene Pighini, Yuji Mishina
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 40
Abstract
Ellis–van Creveld syndrome (EVC) syndrome is a rare genetic disorder affecting skeletal and craniofacial development. The mandibular condyle, a component of the temporomandibular joint (TMJ) essential for jaw movement and craniofacial growth, may be influenced by genetic variation associated with this condition. One gene linked to EVC syndrome is the Evc2 gene, which encodes a protein that regulates the Hedgehog signaling pathway, a signaling pathway critical for cartilage formation and skeletal growth. Proper Hedgehog signaling is required for normal craniofacial cartilage and bone development, including structures of the TMJ. However, mutations in Evc2 can disrupt this pathway and lead to abnormal skeletal development. Our previous studies show that deletion of Evc2 causes structural changes in the mandibular condyle, but the effects of specific amino acid substitutions within the gene remain unclear. This study investigates how genetic variation in Evc2 influences condylar morphology using a global knock-in mouse model. In this model, glycine replaces serine at a conserved amino acid position within the EVC2 protein. This approach allows introduction of a specific amino acid substitution while maintaining the gene’s normal expression pattern during development. Modern humans typically possess serine at this site, whereas Neanderthals carried glycine, a variant associated with more robust craniofacial and mandibular morphology. Based on this evolutionary difference, we hypothesize that the glycine substitution in the Evc2 gene alters mandibular condyle morphology. Therefore, Micro-CT imaging is used to analyze condylar structure, with segmentation performed in ITK-Snap and three-dimensional measurements obtained in 3D Slicer. The sagittal length of the condyle and the anterior, medial, and posterior regions of the intra-articular space between the condyle and temporal bone are quantified. These analyses aim to determine whether variation in the Evc2 gene influences condylar development and may provide insight into craniofacial abnormalities associated with EVC syndrome and related craniofacial disorders.
