Mathematical analysis of mandibular morphogenesis by micro-CT-based mouse and alizarin red S-stained-based human...

Prenatal development of the mandible is an important factor in its postnatal function. To examine quantitatively normal and abnormal developmental changes of the mandible, we here evaluated morphological changes in mineralizing mandibles by thin-plate spline (TPS) including bending energy (BE) and Procrustes distance (PD), and by Procrustes analyses including warp analysis, regression analysis, and discriminant function analysis. BE and PD were calculated from lateral views of the mandibles of mice or of human fetuses using scanned micro-computed tomography (CT) images or alizarin red S-stained specimens, respectively. BE and PD were compared (1) between different developmental stages, and further, to detect abnormalities in the data sets and to evaluate the deviation from normal development in mouse fetuses, (2) at embryonic day (E) 18.5 between the normal and deformed mandibles, the latter being caused by suturing the jaw at E15.5, (3) at E15.5 and E18.5 between normal and knockout mutant mice of receptor tyrosine kinase-like orphan receptor (Ror) 2. In mice, BE and PD were large during the prenatal period and small after postnatal day 3, suggesting that the mandibular shape changes rapidly during the prenatal and early postnatal periods. In humans, BE of the mandibles peaked at 16-19 weeks of gestation, suggesting the time-dependent change in the mandibular shape. TPS and Procrustes analyses statistically separated the abnormal mandibles of the sutured or Ror2 mutant mouse fetuses from the normal mandible. These results suggest that TPS and Procrustes analyses are useful for assessing the morphogenesis and deformity of the mandible.