The Association Between Runx Signaling and Craniofacial Development and Disease

The Runx family genes (Runx1, Runx2, Runx3, and Cbfb) are important transcriptional regulators in the development of various tissues. We herein highlight the roles of the Runx family genes in morphogenesis in the craniofacial regions and in the pathogenesis of congenital morphological problems in these regions.

A recent analysis using conditional Runx mutant animals and a human genetic study identified the novel roles of Runx genes in the development of the tooth, salivary glands, and the palate. In an animal study, Runx1/Cbfb signaling was found to regulate the Lgr5 expression and maintain the stem cells in the dental epithelium in the growing incisors. Aberrant Runx1/Cbfb signaling induced male-specific involution of the convoluted granular cell differentiation of the submandibular gland. In palatogenesis, Runx1/Cbfb signaling regulated the Tgfb3 expression in the fusing palatal epithelium through Stat3 activation. The combination of a human genetic study and a phenotype analysis of mutant animals revealed the various roles of Runx genes in the development of the tooth, palate, and salivary glands. Runx genes have functional redundancy in various tissues, which still hinder the roles of Runx genes in morphogenesis. Future studies may reveal the novel roles of Runx signaling.