Ricerc@Sapienza

Tooth development is a process consisting of formation and eruption steps, that involves a complex interplay of the epithelium with the neural crest derived mesenchyme. Most of the genes involved in tooth development include signalling molecules belonging to BMP, FGF, SHH and WNT pathways. While the role of some genes in tooth development has been elucidated, several aspects related to molecular bases of the odontogenesis are still under investigation. Emerging evidence suggests that also microRNAs (miRNAs) may exert important functions in human dental tissues, whose perturbation could underlie both dental agenesis and eruption process. Dental agenesis is one of the most common dental abnormalities, and dental eruption disturbances are more frequent than the agenesis, with impaction of the maxillary permanent canine as the second most frequent tooth impaction after third molar.
The aim of this project is to study the role of miRNAs in dental anomalies, specifically in canine eruption process. We will focus on DNA variations in miRNAs as genetic determinants of eruption anomalies, both in familiar and sporadic cases, through a combined approach of in silico and experimental studies. The analysis will be performed on already available cases, i.e. a family segregating a phenotype involving the maxillary canines characterized by incomplete penetrance and variable expressivity, and 50 sporadic cases, and will be extended to cases recruited during the project.
This approach will allow to identify and select candidate variants in miRNAs that potentially affect their activity and expression levels, through the alteration of biogenesis and/or targeting.
The identification of functional variants in miRNAs will allow to elucidate molecular bases of tooth agenesis which is a fundamental requirement for genetic counselling and also for the clinical management of dental anomalies, in order to prevent occlusion problems, particularly during developing dentition in children.