Upper jaw development in the absence of teeth: New insights for craniodental evo‐devo integration

Abstract

In p63-null mice (p63 ), teeth fail to form but the mandible forms normally; conversely, the upper jaw skeleton is malformed. Here we explored whether lack of dental tissues contributed to midfacial dysmorphologies in p63 mice by testing if facial prominence defects appeared before odontogenesis failed. We also investigated gene dose effects by testing if one wild type (WT) p63 allele (p63 ) was sufficient for normal upper jaw skeleton formation. We micro-CT scanned PFA-fixed p63 , p63 , and WT (p63 ) adult and embryonic mice aged E10-E14. Next, we landmarked mandibular (MdP), maxillary (MxP) and nasal prominences (NPs), and facial bones. 3D landmark data were assessed using Principal Component, Canonical Variate, Partial Least Squares, and other statistical analyses. The p63 embryos showed MxP and NP malformations by E12, despite the presence of dental tissues. MdP shape was comparable among p63 , p63 , and p63 embryos. Upper jaw shape was comparable between p63 and p63 adults. The upper jaw and its dentition both require p63 signaling, but not each other's presence, to form properly. One WT p63 allele enables normal midfacial morphogenesis; gene dose may be a target for jaw macroevolution. Jaw-specific genetic mechanisms likely integrate the evo-devo of dentitions with upper versus lower jaws.

Expression of new genes in vertebrate tooth development and p63 signaling

“…18 This outcome was not unexpected, as the other six genes-Pltp, Prss8, Krt8, Cldn23, minimally perturbed or unperturbed, and mandibular development is unobstructed. 11,12 Within the p53 family of tumor suppressors, the p63 gene is highly conserved and evolutionarily ancient; p63-like genes and proteins are found in protostomes and deuterostomes. 13 Despite this gene family being named for its first characterized member (p53), p63 most closely resembles the ancestral gene.…”

“…One approach to tease out genes, pathways, and networks for tooth development vs for jaw formation is to study one in the absence of the other. In p63 −/− mice, embryos fail to form tooth placodes, yet the underlying mesenchyme is minimally perturbed or unperturbed, and mandibular development is unobstructed . Within the p53 family of tumor suppressors, the p63 gene is highly conserved and evolutionarily ancient; p63 ‐like genes and proteins are found in protostomes and deuterostomes .…”

“…Our recent cDNA gene expression screen comparing transcript levels between mandibular prominences of normal ( p63 +/− ) and toothless ( p63 −/− ) mouse genotypes aged E10.5 to E13.5 flagged more than 32 genes with significant, large expression differences in the p63 −/− samples . Collectively, these genes comprise a putative gene regulatory network (GRN) controlled by master transcription factor p63 that appears to be specific to odontogenesis and superfluous to jaw development . This nascent GRN offers the capacity to study jaws separately from teeth, and implicates for the first time many additional genes in odontogenesis and p63 expression (Figure ).…”

“…18 Collectively, these genes comprise a putative gene regulatory network (GRN) controlled by master transcription factor p63 that appears to be specific to odontogenesis and superfluous to jaw development. 11,12,18 This nascent GRN offers the capacity to study jaws separately from teeth, and implicates for the first time many additional genes in odontogenesis and p63 expression ( Figure 1). As such, we have investigated this putative GRN further.…”

Genetic influences on dentognathic morphology in the Jirel population of Nepal

“…Yet evolutionary, developmental, and molecular studies have also demonstrated a degree of independence between tooth and jaw formation (Boughner & Hallgrimsson, 2008). For example, p63 is essential for both dental and upper jaw development but not lower jaw development (Phen et al, 2018; Raj & Boughner, 2016). The co‐occurrence of orofacial clefting and tooth agenesis also demonstrates the co‐dependence of some aspects of jaw and tooth genetic regulation and development (Phan et al, 2016).…”