Making up the numbers: The molecular control of mammalian dental formula

Abstract

Teeth develop in the mammalian embryo via a series of interactions between odontogenic epithelium and neural crest-derived ectomesenchyme of the early jaw primordia. The molecular interactions required to generate a tooth are mediated by families of signalling molecules, which often act reiteratively in both a temporal and spatial manner. Whilst considerable information is now available on how these molecules interact to produce an individual tooth, much less is known about the processes that control overall tooth number within the dentition. However, a number of mouse models are now starting to provide some insight into the mechanisms that achieve this. In particular, co-ordinated restriction of signalling molecule activity is important in ensuring appropriate tooth number and there are different requirements for this suppression in epithelial and mesenchymal tissues, both along different axes of individual jaws and between the jaws themselves. There are a number of fundamental mechanisms that facilitate supernumerary tooth formation in these mice. A key process appears to be the early death of vestigial tooth primordia present in the embryo, achieved through the suppression of Shh signalling within these early teeth. However, restriction of WNT signalling is also important in controlling tooth number, with increased transduction being capable of generating multiple tooth buds from the oral epithelium or existing teeth themselves, in both embryonic and adult tissues. Indeed, uncontrolled activity of this pathway can lead to the formation of odontogenic tumours containing multiple odontogenic tissues and poorly formed teeth. Finally, disrupted patterning along the buccal-lingual aspect of the jaws can produce extra teeth directly from the oral epithelium in a duplicated row. Together, all of these findings have relevance for human populations, where supernumerary teeth are seen in association with both the primary and permanent dentitions. Moreover, they are also providing insight into how successional teeth form in both embryonic and post-natal tissues of the jaws.