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.

中文翻译：

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在没有牙齿的情况下上颌骨的发育：颅牙evo-devo融合的新见解。

在p63无小鼠（p63 ^-/-）中，牙齿无法形成，但下颌骨正常形成。相反，上颌骨骨骼畸形。在这里，我们通过测试在牙源发生失败之前是否出现了面部突出缺陷，来探讨缺乏牙齿组织是否会导致p63 ^-/-小鼠的面中畸形。我们还通过测试一种野生型（WT）p63等位基因（p63 ^+/-）是否足以正常上颌骨形成来研究基因剂量效应。我们用microCT扫描了PFA固定的p63 ^-/-，p63 ^+/-和WT（p63 ^{+ / +}）成年和E10-E14岁的胚胎小鼠。接下来，我们对下颌骨（MdP），上颌骨（MxP）和鼻隆起（NPs）以及面部骨骼进行标记。使用主成分，规范变量，偏最小二乘和其他统计分析来评估3D地标数据。尽管存在牙齿组织，但p63 ^-/-胚胎通过E12仍显示MxP和NP畸形。MdP形状在p63 ^-/-，p63 ^+/-和p63 ^{+ / +}胚胎之间具有可比性。上颚形状在p63 ^{+ / +}和p63 ^+/-之间可比成年人。上颌及其牙列都需要p63信号，但不需要对方的存在才能正确形成。一个WT p63等位基因可使正常的面部形态发生。基因剂量可能是颌大进化的目标。颚特有的遗传机制可能将牙列的进化与上颚和下颚结合在一起。