Shark tooth regeneration: RNAseq reveals genes for unlimited dental renewal

Sharks are masters of tooth regeneration with a rapid and unlimited tooth supply. We present a comprehensive transcriptomic analysis across five distinct compartments from the embryonic shark mouth, capturing the full sequence of shark tooth development. Differential gene expression and gene regulatory network analyses reveal novel candidate markers upregulated within epithelial stem cells of the dental lamina. We show a potential role for this conserved regenerative network in the regulation of tooth production in sharks. Notably, we find the proto-oncogene mycn co-expressed with a definitive dental stem cell marker, sox2 . Perturbation of mycn disrupts stem cell proliferation, underscoring its role in regulating dental stem cells in sharks. Our data showcase the power of transcriptome-based developmental approaches in the identification of predictive gene networks governing unlimited dental regeneration. The shark dental lamina provides an accessible system for the study of regeneration, offering exciting opportunities for investigating translational mechanisms of natural tooth renewal.