An ancient dental gene network regulates development and continuous regeneration of teeth in sharks

The appearance of toothed vertebrates has proven a major determinant of the overall success of this lineage. This is most apparent in sharks and rays (elasmobranchs), which further retain the capacity for life-long tooth regeneration. Given their comparatively basal phylogenetic position, elasmobranchs therefore offer the opportunity for crucial insights into putative ancestral characters of tooth development, yet despite their evolutionary significance this remains poorly understood. Using the established chondrichthyan model, the catshark (Scyliorhinus sp.), we identified the expression of genes representative of conserved signaling pathways during stages of early dental competence, tooth initiation and regeneration. The expression patterns of β-catenin, shh, bmp4, pax9, pitx1/2, and the stem cell marker Sox2, characterise an ancestrally conserved gene set deployed during initiation of the elasmobranch dentition, suggesting that all vertebrate dentitions are defined by the expression of this core set of genes. These findings provide novel evidence to support the conservation in deep evolutionary time of a core set of dental patterning genes, therefore further defining the evolutionary trajectory of tooth development. We show how these genes facilitate the emergence of the shark dentition and offer insights into their deployment during development of the dental lamina, a sheet of dental epithelial cells that are responsible for continuous tooth regeneration. This study further promotes a specific experimental agenda to further characterise the roles of these core developmental genes during vertebrate tooth development, and importantly dental regeneration