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

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.