Ashley Dixon
Pronouns: she/her
Research Mentor(s): Renny Franceschi
Research Mentor School/College/Department: Periodontics & Oral Medicine, Biological Chem-Medical School / Dentistry
Program: UROP
Session: Session 5 (2:40pm – 3:30pm)
Authors: Danny Dixon, Lisa Levinson
Abstract
The Runt-related transcription factor 2 (Runx2) protein orchestrates bone formation in vertebrates. Loss of Runx2 is not sustainable with life, while deletion of one copy of Runx2 results in cleidocranial facial dysplasia, a rare condition characterized by midfacial hypoplasia, supernumerary teeth and clavicular hypoplasia. The focus of this research is to study the function of Runx2 in the cranial base, a bone resting between the mandible and calvarium in the skull. Within the cranial base lies the cartilaginous growth centers, the spheno-occipital synchondrosis (SOS) and the intersphenoid synchondrosis (ISS), which are composed of pre-chondrocytes. Importantly, activation of synchondrosis chondrocytes promotes anteroposterior growth of the cranial base and the entire craniofacial complex. Removing one copy of Runx2 in a specific subset of chondrocytes, marked by a negative regulator of endochondral bone development, Fibroblast growth factor receptor 3 (Fgfr3) allows us to observe its role in cranial base development. Notably, overactivation of Fgfr3 in humans and mice causes early fusion of the cranial base due to precocious ossification of the synchondroses. This research is executed by harvesting tissues from both wildtype and mutant mice ranging from one to twenty-one days after birth, then sectioning the harvested cranial bases and noting the difference in synchondroses growth. Hematoxylin and eosin stains cellular nuclei so the distribution of cells within the tissue is more easily observed. It was previously found that mutant mice at one month of age possess abnormal craniofacial features. Therefore, we aim to pinpoint the period when these phenotypes emerge. In normal development, Runx2 is an inhibitor of Fgfr3, which itself is an inhibitor of growth plates. From the data collected so far, we noticed that conditional deletion of Runx2 in chondrocytes in mice resulted ins over-expression of Fgfr3, suggesting Runx2 has an inverse relationship with the Fgfr3 protein.
