The Role of Notch Pathway in Tooth Root Formation

Abstract

During this PhD project I aimed to unravel the role of Notch signalling in tooth root formation. Teeth are essential for overall well-being and have crucial functions including mastication, speech, facial aesthetics and self-perception. Odontogenesis is a complex process tightly controlled by various evolutionary conserved signalling pathways which establish tooth morphogenesis, cytodifferentiation, mineralization and regeneration. The dental integrity is assured by the proper development of the tooth root that provides the stability and integrity to the tooth. The cellular and molecular mechanisms of tooth root formation have not been fully elucidated yet. Tooth root development is initiated by the formation of the root epithelium, which is currently hypothesized to derive from the outer and inner enamel epithelium layers of the tooth crown. The Notch signalling pathway is a well-established regulator of dental cell fates, cell differentiation, and mineralization during tooth crown formation. Notably, Notch molecules have been detected during the formation of the tooth root epithelium. However, the specific role of the Notch pathway in cell fate decisions, and its involvement in the molecular regulation of root development remains poorly understood. In this thesis, I address these questions using mouse molars, which develop roots and serve as an excellent model for investigating the molecular and cellular mechanisms governing root development. My work mainly focused on the analysis of early stages of tooth root development. Specifically, I investigated the distribution of various Notch pathway components in the developing root and examined the contribution of Notch expressing cell populations to the root epithelium. Additionally, I studied the role of Notch signalling in the molecular regulation of root development. To achieve this, I utilized transgenic mouse lines, including reporter lines, lines for targeted cell ablation, Cre lines, and mutant lines. These were processed for histomorphological analyses, immunostaining, confocal imaging, microCT scanning, and ex vivo organ cultures. My data demonstrate the role of Notch signalling in tooth root formation. $\textit{Full-text embargoed until: 2026-03-05}$