The Role of GSK3 alpha and beta in Embryonic Craniofacial Development

Background: The GSK-3 genes (Gsk3a and Gsk3b) have been known to affect many cellular processes and signaling pathways some of which are implicated in the growth and development of the craniofacial skeleton. Aim: The purpose of this study was to assess the effect of chondrocyte-specific deletion of Gsk3a and Gsk3b on the size of the mandible and craniofacial skeleton in embryonic mice. Materials & Methods: Mice were bred to generate cartilage-specific Gsk3a and Gsk3b KO mice. On embryonic day 18.5 (E18.5) the offspring were gathered by caesarian section. Whole mount skeletal staining was completed on the specimens using Alcian blue and Alizarin red. The antero-posterior (AP) dimension of the entire craniofacial skeleton and the mandible was measured, along with the transverse dimension of the cranial vault and the intramandibular angle for each embryo. The investigator was blind to the genotype of embryos in each trial group. Immunohistochemistry was used to detect and localize three proteins, Sox9, Beta-catenin, and Osteocalcin, in the bone and cartilage of E16 mouse skulls. Results: The specific removal of both Gsk3a and Gsk3b in prenatal cartilage of mice leads to a significant reduction in the antero-posterior length of the total craniofacial skeleton and mandible when compared to wildtype mice. Cartilage-specific Gsk3a/Gsk3b KO mouse embryo display no significant change in the transverse width of the cranial vault. A significant increase in the intramandibular angle is seen in the KO mice when compared to the wild type mice. Conclusions: Loss of both GSK-3 isoforms in prenatal mice results in significant changes to the size and shape of the facial skeleton and cranium