A forward genetic screen for genes regulating mineralized tooth and bone formation in zebrafish (Danio rerio)

P>Our laboratory studies craniofacial skeletal and tooth regeneration. One approach we are using is to exploit the zebrafish model via a large-scale, forward genetic, chemical N-ethyl-nitroso-urea (ENU) mutagenesis screen to identify genes regulating mineralized craniofacial, axial and dental development. The fact that zebrafish continuously regenerate their teeth makes them an extremely useful model to study tooth regeneration. Our goal is to identify and characterize molecular genetic signaling pathways regulating these processes, which can be manipulated via targeted gene delivery strategies. Through these efforts, we hope to eventually define methods for effective, clinically relevant bone and tooth replacement therapies in humans. Here, we describe our studies using the zebrafish model, which are proving to be useful for the identification and characterization of genes regulating mineralized tissue formation, regeneration, and homeostasis. Although preliminary at the present time, we anticipate the elucidation of novel signaling pathways regulating bone and tooth regeneration, which will eventually facilitate the repair of human skeletal and dental dysplasias.