Tooth Replacement in an Anatomical Context: Studies in the Zebrafish

Most non‐mammalians that possess teeth display lifelong tooth renewal. So far, studies aiming to dissect the mechanisms underlying continuous tooth replacement have focused mostly on the molecular cues that may regulate replacement. However, if we wish to fully understand this process, we also need to consider the cellular environment in which teeth develop. We have embarked on studies investigating the vasculature and innervation of the zebrafish pharyngeal dentition (there are no oral teeth), and their respective roles in tooth replacement, using light microscopy, 3D reconstructions and immunohistochemistry. First, we have demonstrated that, while the first‐generation teeth develop before the vasculature has reached the last pharyngeal arch on which these teeth develop, functional teeth become surrounded by an elaborate sinusoidal cavity. Capillaries branching off from this sinusoidal vessel supply replacement teeth at an advanced stage in their development, as they enter the pulp cavity only at late cytodifferentiation. Blocking VEGF, a major angiogenic factor, slows down replacement tooth development but does not prevent initiation of new teeth, suggesting that formation of new blood vessels does not trigger the replacement process. Like the more anterior, gill‐bearing arches, the dentigerous pharyngeal arch is innervated by posttrematic rami of the vagal nerve (NX). Sensory fibers enter the pulp cavity at a late stage of cytodifferentiation, shortly before attachment of the tooth. Autonomous fibers have not been identified so far. Whether nerves follow the vasculature in entering the pulp, as in mammalian teeth, and what the role is of the neurovascular supply in teeth that are renewed anyway, needs further studies. This study was supported by a grant of the IWT‐Vlaanderen to JC.