The epithelial-mesenchymal interaction plays an important role in craniofacial development.It is spatiotemporally regulated by growth and transcription factors and adhesion molecules.Fibroblast Growth Factor (FGF) signaling plays a curial role in not only early gastrulation, but also organogenesis and development related to the epithelial-mesenchymal interaction.We developed epithelial tissue inactivation in fgfr1 or fgfr2 mice. Abnormal tooth calcification and attrition were observed epithelial tissue inactivation in the fgfr1 mouse, and the same symptoms were noticed in the patient with Kallmann syndrome.Epithelial tissue inactivation in the fgfr2 mouse resulted in anomalies of the ears, digits, tooth initiation, and palate development. These are the same symptoms observed in a patient with lacrimoauriculo-dento-digital (LADD) syndrome. A cleft palate and delay in tooth development were observed inactivation in FRS2α mouse.These results revealed that the epithelial and mesenchymal FGF signal plays a curial role in organogenesis and development of the craniofacial region. Genetically modified animals were useful for investigating the cause and determining the therapy of hereditary disorders.