Retinoic Acid Signaling and the Zebrafish Dentition During Development and Evolution.

Explaining how the extensive diversity in form of vertebrate teeth arose in evolution and the mechanisms by which teeth are made during embryogenesis are intertwined questions that can merit from a better understanding of the roles of retinoic acid (RA) in tooth development. Pioneering studies in rodents showed that dietary vitamin A (VA), and eventually RA (one of the major active metabolites of VA), are required for proper tooth formation and that dentin-forming odontoblast cells seem to be especially sensitive to changes in RA levels. Later, rodent studies further indicated that RA signaling interactions with other cell-signaling pathways are an important part of RA's actions in odontogenesis. Recent investigations employing zebrafish and other teleost fish continued this work in an evolutionary context, and specifically demonstrated that RA is required for the initiation of tooth development. RA is also sufficient in certain circumstances to induce de novo tooth formation. Both effects appear to involve cranial-neural crest cells, again suggesting that RA signaling has a particular influence on odontoblast development. These teleost studies have also highlighted both evolutionary conservation and change in how RA is employed during odontogenesis in different vertebrate lineages, and thus raises the possibility that developmental changes to RA signaling has led to some of the diversity of form seen across vertebrate dentitions. Future progress in this area will come at least in part from expanding the species examined to get a better picture of how often RA signaling has changed in evolution and how this relates to the evolution of dental form.