Transcription factors involved in ameloblast proliferation, differentiation and maturation. Transcription factors involved in ameloblast proliferation and differentiation (in black), and hormonal response (in blue). Enamel gene patterns are linked to presecretion, secretion and maturation stages of amelogenesis. The first key-point is the transition from presecretion to secretion stage during which differentiated ameloblasts acquire all the properties required for orderly secretion of enamel proteins (amelogenin, enamelin, amelobastin, and calbindin-D28k). A subsequent key-point for amelogenesis is the second transition from secretion to post-secretion. This event determines final enamel thickness via an abrupt decrease in matrix protein production. Enamel mineral quality is also conditioned by this transition associated with massive cell apoptosis and size reduction. Ameloblasts show an abrupt increase in the production of proteins involved in the mineralization process, including MMP20 and KLK4 proteases, mineral-handling effectors such as Ca-ATPase, alkaline phosphatase, proton pumps, carbonic anhydrase, calbindin-D28k, and tight junction elements which contribute to enamel maturation. The list of up- and down-regulated genes at these two key stages of amelogenesis is emerging from current “omics” studies and most of them have been identified. The challenge now will be to integrate these effectors and their regulators into a model that describes the resulting enamel quality. CL, cervical loop; PS, pre-secretion; S, secretion; T, transition; M, maturation stages and P, pigmentation. (1, Golonzhka et al., 2009; 2, Yasukawa et al., 2013; 3, Cao et al., 2013; 4, Catón et al., 2009; 5, Xu et al., 2007a; 6, Athanassiou-Papaefthymiou et al., 2011; 7, Stahl et al., 2013; 8, Zhou and Snead, 2000; 9, Lézot et al., 2008; 10, Bei et al., 2004; 11, Molla et al., 2010; 12, Yanagawa et al., 2004; 13, Muto et al., 2012; 14, Ferrer et al., 2005; 15, Bloch-Zupan et al., 1994; 16, Lacruz et al., 2012b; 17, Sahlberg et al., 2002; 18, Davideau et al., 1996; 19, Bei, 2009).