AN ANCESTRAL GENE NETWORK REGULATES CONTINUOUS TOOTH REGENERATION AND DENTICLE DEVELOPMENT IN ELASMOBRANCHS

Sharks and rays (elasmobranchs) regenerate their teeth via a novel system in which multiple teeth develop in advance of function as a dental conveyor belt. Given their ancestral phylogenetic position, extant elasmobranchs therefore provide ideal models to study the ancient state of gnathostome tooth regeneration (polyphyodonty). Despite this potential, they have received little attention, leaving a significant gap in knowledge. The research presented here addresses this by using suitable species of catshark and ray as comparative models to investigate conserved gene expression during elasmobranch tooth development and regeneration. In both sharks and rays, the conserved expression patterns of the dental stem cell marker Sox2 first identifies a putative dental stem cell niche (SCN). Using the catshark as a primary model, PCNA is then used to define cell proliferation dynamics, followed by further investigation of the expression of genes representative of the Wnt-β-catenin, BMP, FGF and hedgehog signaling pathways. Their expression patterns, and those of additional regulatory genes, imply deeply conserved roles in the elasmobranch dentition. This is particularly apparent in tooth morphogenesis in which the expression of several genes identifies a putative signaling center comparable to the mammalian enamel knot. PCNA and gene expression further define a continuous epithelial connection between the dental and oral epithelium, adding further experimental evidence to support the role of a dental SCN in elasmobranch tooth regeneration. These studies inspire the production of the first hypothetical elasmobranch dental gene regulatory network (GRN) models. This research further addresses the role of conserved genes in the development of dermal denticles, which in chondrichthyans enhance hydrodynamic efficiency and function as dermal body armour. These gene expression patterns imply similar regulatory roles to those in teeth, suggesting their evolution by a mechanism of gene network co-option. This further inspires the production of a denticle GRN model. When considered in light of existing theories of tooth and denticle evolution, this comparative expression data adds renewed perspective regarding their possible origins, as implied by their respective developmental similarities and differences.