Cranial neural crest cells considerably contribute to the formation of craniofacial structures during embryogenesis. Like many other organs, teeth develop through a series of reciprocal interactions between two adjacent tissues, the epithelium and the mesenchyme, most of which are cranial neural crest cells migrated from neural folds. Cranial neural crest cells migrate from dorsal to ventral under the epithelium, and some of them reside into the developing first pharyngeal arch. It has been suggested that NGF is required for the migration and/or differentiation of cranial neural crest cells. The expression patterns of neurotrophins including NGF and their cognate receptors suggest that they have some effects on tooth formation. However, the biological role of neurotrophins in the development of non-neural tissues such as tooth germ remains unclear. An low-affinity receptor for NGF, p75 is expressed in many embryonic organs, and has been proposed to have regulatory roles or functions during the development of non-neural tissues. High-affinity NGF receptor trkA is not expressed in the region of tooth formation, while p75 low-affinity NGF receptor is expressed in the mesenchyme of first pharyngeal arch at the stage of tooth initiation.
In this study, organ culture system of E9 mouse mandibles and antisense inhibition technique of p75 low-affinity neurotrophin receptors have been used to study the effects of NGF signals on the cranial neural crest cells. Cultured for 10 days, control groups supplemented with p75 random oligonucleotides and groups with no supplementation formed tongue, Meckel's cartilage and cap stage tooth germ, while no tooth germs were observed in the explants cultured with the antisense oligonucleotides. Results of this study suggest that NGF signal is required for the cranial neural crest cells, which form dental mesenchyme, and is mediated through p75.