Host: Yoshiyuki Yamamoto

The dentition of fishes exhibits enormous diversity in shape, number, and location of individual teeth. My laboratory is investigating the developmental mechanisms underlying this diversity through comparisons of gene expression and function between the zebrafish, Danio rerio, and the related Mexican blind cave tetra, Astyanax mexicanus. Teeth in the zebrafish are restricted to the posterior pharynx, while the Mexican tetra possesses both oral and pharyngeal teeth. In addition, while all teeth of the zebrafish are unicuspid, many of the oral teeth of the Mexican tetra are multicuspid. We have identified several genes whose oral expression has been lost in association with evolutionary loss of oral teeth in the zebrafish lineage. We used reporter transgenesis to investigate the mechanism of expression loss for one of these genes, the transcription factor dlx2b, and found evidence for change in its trans-acting regulators. Transgenic misexpression of candidates for these regulators, ligands of the Fibroblast growth factor (Fgf) family, failed to induce oral teeth in the zebrafish, but resulted in supernumerary, and occasionally multicuspid, teeth in the pharyngeal region of both the zebrafish and Mexican tetra. These results suggest that loss of oral teeth in the zebrafish lineage is associated with restriction of competence to respond to tooth initiation signals and that the evolutionary origin of multicuspid teeth may have involved relatively simple genetic changes. The tooth phenotypes produced by ectopic expression of Fgfs qualitatively resemble those predicted by reaction-diffusion models for the control of the spacing of vertebrate ectodermal appendages (e.g. feathers and hairs), and such models are further supported by the effects of pharmacological inhibition of Bone morphogenetic protein (Bmp) signaling in the Mexican tetra.