Preameloblasts overtly differentiate in vitro when recombined with cell-free predentin-dentin. The predentin-dentin components able to trigger ameloblast terminal differentiation have not been identified, but some growth factors (members of the TGFbeta superfamily) have been demonstrated to be associated with this matrix, and in situ hybridization has demonstrated the presence of transcripts for TGFbetas and BMP-2 in odontoblasts facing differentiating ameloblasts. Moreover, intense expression of receptors for the cytokine interleukin-7 (IL-7) in polarizing ameloblasts has been reported. In this study, isolated E-18 and E-19 mouse molar enamel organs were cultured in vitro in presence of BMP-2, TGFbeta-1, IL-7 or synthetic apatite. TGFbeta-1 and BMP-2 combined with heparin induced cytodifferentiation of ameloblasts. IL-7 maintained the polarized state of ameloblasts. BMP-2-soaked apatite induced functional differentiation of ameloblasts (secretion of amelogenin). Integrating these data with previous work, a working hypothesis concerning the control of ameloblast terminal differentiation is presented: members of the TGFbeta superfamily secreted by odontoblasts might be trapped by predentin components first and then by dentin apatites, and these growth factors might trigger the cytological-functional sequence of ameloblast terminal differentiation.