Temporal-spatial Expression And Roles Of Tcf12 In Tooth Development

Tooth development is dependent on a variety of transcription factors that regulate the interaction between epithelial and mesenchymal cells.Transcription factor 12(TCF12)is a basic helix-loop-helix(bHLH)partner of TWISTl whose mutation plays a vital role in coronal suture development due to the dosage of TCF12/TWIST1 heterodimers.In addition,the essentiality of Twistl during tooth morphogenesis and odontoblast differentiation has also previously been characterized.However,no report to date has investigated the specific role of Tcf12 during this process.In the present study,we investigated the effect of Tcfl2 during the tooth mineralization process by utilizing first molars from mouse embryos for organ culturing,as well as by culturing LS-8 mouse-derived ameloblast-like cell line in vitro.Our data demonstrates strong expression of Tcfl 2 in developing tooth germs,particularly in the epithelial layers that then progress into the enamel knot;a signaling center for tooth morphogenesis.We then shown in knock-down and knock-in cell culture experiments using siRNA that Tcf12 is responsible for gene expression representative of amelogenesis.We further utilized first molar tooth buds transfected with siRNA to over-/under-express Tcf12 and further demonstrate its prominent role in the mineralization process of ameloblasts.Overall,we draw the conclusion that Tcf12 is critical for tooth development and acts as a pro-amelogenesis transcription factor.