P63 expression plays a role in developmental rate, embryo size, and local morphogenesis

Abstract

Background: The p63 gene is integral to the development of many body parts including limb, palate, teeth, and urogenital tract. Loss of p63 expression may alter developmental rate, which is crucial to normal morphogenesis. To validate a novel, unbiased embryo phenotyping software tool, we tested whether delayed development contributes to the pathological phenotype of a p63 mouse mutant (p63^-/- ). We quantified dysmorphology in p63^-/- embryos and tested for universal growth delay relative to wild-type (WT) embryos. Fixed embryos (n = 6; p63^-/- ) aged day (E) 15.5 were micro-CT scanned and quantitatively analyzed using a digital WT atlas that defined volumetric differences between p63^-/- and WT embryos.

Results: p63^-/- embryos showed a growth delay of approximately 22 hr (0.9 days). Among the E15.5 mutants, overall size was closest to WT E14.6 mice but shape was closest to WT E14.0. The atlas clearly identified in p63^-/- embryos malformations of epithelial derivatives including limbs, tail, urogenital structures, brain, face, and tooth.

Conclusions: The software atlas technique described the p63^-/- phenotype as a combination of developmental delay (i.e., heterochrony) and malformation (i.e., pathological shape; failed organogenesis). This study identifies for the first time global and local roles for p63 in prenatal growth and development. Developmental Dynamics 247:779-787, 2018. © 2018 Wiley Periodicals, Inc.

Keywords: 3D imaging; 4D Atlas; Tp63; Trp63; heterochrony; micro-CT; mouse; organogenesis.