The ability to form teeth was lost in an ancestor of all modern birds, approximately 100-80 million years ago. However, experiments in chicken have revealed that the oral epithelium can respond to inductive signals from mouse mesenchyme, leading to reactivation of the odontogenic pathway. Recently, tooth germs similar to crocodile rudimentary teeth were found in a chicken mutant. These "chicken teeth" did not develop further, but the question remains whether functional teeth with enamel cap would have been obtained if the experiments had been carried out over a longer time period or if the chicken mutants had survived. The next odontogenetic step would have been tooth differentiation, involving deposition of dental proteins.

Using bioinformatics, we assessed the fate of the four dental proteins thought to be specific to enamel (amelogenin, AMEL; ameloblastin, AMBN; enamelin, ENAM) and to dentin (dentin sialophosphoprotein, DSPP) in the chicken genome. Conservation of gene synteny in amniotes allowed definition of target DNA regions in which we searched for sequence similarity. We found the full-length chicken AMEL and the only N-terminal region of DSPP, and both are invalidated genes. AMBN and ENAM disappeared after chromosomal rearrangements occurred in the candidate region in a bird ancestor.

These findings not only imply that functional teeth with enamel covering, as present in ancestral Aves, will never be obtained in birds, but they also indicate that these four protein genes were dental specific, at least in the last toothed ancestor of modern birds, a specificity which has been questioned in recent years.