Elucidation of tooth patterning and development

In humans, teeth are important for many aspects of our lives, from social interactions to feeding, making tooth-related abnormalities devastating at times. Unlike bones, teeth have almost no regenerative ability, making the use of prostheses the only restorative approach in cases of tooth deterioration However, the development of more biologically-compatible implants is impaired by the limited knowledge of the mechanisms behind tooth shaping and growth. This project aims at globally define the factors involved in the decision of tooth shape and in their proper development. Using these information, we will recapitulate tooth development in vitro. This project will provide the community with a thorough road map of the developing tooth as well as define the factors involved in the shape of the teeth. These data will be crucial for tooth bioengineering. We have preliminary results suggesting an important role of the peripheral nervous system (PNS) in tooth induction and the choice of its shape. The candidate will analyze tooth development in a model with no tooth innervation. This will be done through advanced imaging techniques, including state of the art confocal/light-sheet microscopy and micro computed tomography. Using next generation sequencing, we will determine the potential mechanisms through which the PNS influences tooth patterning and development. These experiments have the potential to define a new role of the PNS in the shaping of teeth. As the PNS is not the only player in tooth development, we will analyze gene expression at the cell level during tooth development. Using the last development in bioinformatics, we will draw a developmental trajectory of all the cell types participating to tooth formation from the expression data. These data will also provide information on the signals the different cell types can be responsive to during the development of the tooth. Using imaging, we will spatially define the expression of the key receptors involved in cell differentiation. We will also define the potential origin of the signals the cells of the developing tooth are responsive to. These experiments will globally define, in an unbiased way, all the factors behind tooth shape and development. Finally, using the factors defined above, the candidate will attempt at recapitulating tooth development in vitro. He will cultivate biopsies possessing divers abilities to generate tooth in the mouse embryo. He will treat them either through global treatment or local treatment by beads loaded with different factors. Using histology and confocal imaging, he will assess the effect of these factors on tooth development. These experiments will be an important step towards the design of smart scaffolds for the production of biologically functional tooth implants.