Contribution of mesoderm to the developing dental papilla

Teeth develop from epithelium and neural crest-derived mesenchyme via a series of reciprocal epithelial-mesenchymal interactions. The majority of the dental papilla of the tooth has been demonstrated to be of neural crest origin. However, non-neural crest cells have also been observed in this region from the bud stage of tooth development onwards. The number of these non-neural crest-derived cells rises as the dental papilla develops. However, their origin is unknown. We have followed migration of cells into the tooth in vitro using DiI to fate map regions surrounding the developing tooth. To identify the contribution of mesodermally-derived cells, we have utilised Mesp1cre/R26R transgenic reporter mice. We document that cells outside the early tooth primordium migrate into the developing dental papilla from the late cap stage of development. Here, we show that migrating cells are mesodermally-derived and create a network of endothelial cells, forming the blood vessels of the tooth. No cells of mesodermal origin were present in the condensed mesenchyme surrounding the dental epithelium until the cap stage of tooth development. Mesodermally-derived cells start invading the dental papilla at the late cap stage, providing the blood supply to the dental pulp. Endothelial cells are able to invade the developing dental papilla in vitro using the slice culture method. Understanding the origin and timing of migration of the mesodermally-derived cells is an important advance in our understanding of how a tooth develops and is particularly relevant to studies which aim to create bioengineered teeth.