Jaw growth in the absence of teeth: the developmental morphology of edentulous mandibles using the p63 mouse mutant

Abstract

Mammalian tooth and jaw development must be coordinated well enough that these systems continue to function together properly throughout growth, thus optimizing an animal's survival and fitness, as well as a species' success. The persistent question is how teeth and jaws remain developmentally and functionally viable despite sometimes monumental evolutionary changes to tooth and jaw shape and size. Here we used the p63 mouse mutant to test the effect of tooth development - or the lack thereof - on normal mandible developmental morphology. Using 3D geometric morphometrics, we compared for the first time mandible shape among mice with normal tooth and jaw development against p63 double knock-out mice, with failed tooth development but apparently normal jaw development. Mandible shape differed statistically between toothless (p63(-/-) ) and toothed (p63(+/-) , p63(+/+) ) mice as early as embryonic day (E) 18. As expected, most of the shape difference in the p63(-/-) mandibles was due to underdeveloped alveolar bone related to arrested odontogenesis in these E18-aged mice. Mandible shape did not differ statistically between p63(+/-) and p63(+/+) adult mice, which showed normal tooth development. Our results support the idea of a gene regulatory network that is exclusive to the mandible and independent of the dentition. This study also underscores the biomechanical impact of the teeth on the developing alveolar bone. Importantly, this work shows quantitatively that the p63 mutant is an apt model with which to study mandible morphogenesis in isolation of odontogenesis to clarify developmental relationships between the teeth and jaws.