Molecular Mechanisms Regulating Tooth Number

Abstract

Tooth number, shape, and position are consistent in mammals and are subject to strict genetic control. Multiple signaling pathways including Shh, Tgf, Bmp, Wnt, Fgf, Notch, and NF-kB are known to play critical roles in regulating tooth development. Recent studies show that these signaling pathways interact with each other through positive and negative feedback loops to regulate tooth number, shape, and spatial pattern. Teeth develop via a dynamic and complex reciprocal interaction between dental epithelium and cranial neural crest-derived mesenchyme. These interactions contain a series of inductive and permissive processes that lead to the determination, differentiation, and organization of odontogenic cells, which are controlled by these signaling pathways. It is believed that dozens of different molecules together form complex molecular networks that regulate tooth development. Studies of human congenital disease and transgenic mice suggest that disturbance of the molecular network results in abnormal tooth formation. Since molecular mechanisms involved in tooth development should be reproduced in tooth regeneration, knowledge of tooth development from both human and mouse studies is crucial for exploring tooth regenerative therapies. In this paper, we present an overview of the current literature covering the molecular mechanisms of tooth development, especially those regulating tooth number.