Abstract： At the early stage of tooth development, the tooth embryo underwent three successive stages: bud stage, cap stage and bell stage through the interaction between epithelium and mesenchymal cells. During these stages, especially during the interphase transition, the presence of signal centers was particularly crucial. Signal center was composed of a small group of oral epithelial cell collections which were formed in a specific sequence, playing a decisive role in signal expression, morphogenesis and cell differentiation by secreting growth factors and other signaling molecules to regulate developmental signaling pathways. This paper reviews the evolution of signal centers as well as the important signal molecules and transcription factors in signal centers since the formation of dental placode.