Runx1 is involved in palatogenesis

Objectives: Runx1 form a heterodimer with CBFß, which is required for both hematopoiesis. Although a function for Runx1 has only been established in hematopoiesis, Runx1 is also expressed in the palatal shelf epithelium. At E14 prior to horizontalization of the shelves, the expression is more intense and localized to the tips of the shelves which contact in the midline at E14.5. This expression suggested the possible roles of Runx1 in palatal fusion, however Runx1 null mutants die between E10.5 and E12.5 because of hemorrhaging in its brain ventricles before a palatal phenotype would appear. In the present study, hemorrhage in Runx1 null mutants was rescued by Runx1 overexpression under Gata1 promoter, and we evaluated palatal phenotypes in this conditionally rescued knockout mice. Methods: E17.5 heads were fixed in 4% buffered formalin after they were assessed for palatal fusion. To confirm palatal fusion at the histological level, heads were embedded in paraffin. Coronal sections were prepared serially from anterior to posterior and processed for HE staining. Results: Runx1-/-/Gata1-Runx1 mice newborns were assessed for palate fusion by direct observation with a dissecting microscope. Runx1-/-/Gata1-Runx1 mice showed partial cleft fusion. The palate was unfused between the primary and the secondary plates and between secondary plates at 1st Ruga. Palatal fusion was also verified microscopically by examining serial histological sections of the secondary palates. In Runx1-/-/Gata1-Runx1 mice, the secondary palate and the nasal septum were not fused. Conclusion: These findings indicated that Runx1 is involved in fusion between the primary and secondary palates and between the secondary palate and the nasal septum. This study was supported by a Grant-In-Aid for Scientific Research from Japan Society for the Promotion of Science.