Chapter category: Development
Signaling Loops in the Reciprocal Epithelial-Mesenchymal Interactions of Mammalian Tooth Development
Molecular Basis of Epithelial Appendage Morphogenesis
Edited by: Cheng-Ming ChuongISBN: 1-57059-490-2
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Chapter authors:
Yi-Ping Chen and Richard Maas
Organogenesis is a complex process that results from sequential and reciprocal cell and tissue interactions. Tooth development, which shares similarities with the development of other embryonic organs, is characterized by a series of reciprocal epithelial-mesenchymal interactions that result in the differentiation and organization of the interacting tissues. Therefore, mammalian tooth development provides an excellent model for studying epithelial-mesenchymal interactions. The recent combination of molecular biology and classical experimental embryology has begun to elucidate the molecular mechanisms of such interactions in tooth morphogenesis. In situ hybridization and immunochemical analysis have revealed the expression of growth factors such as BMPs, FGFs, and other signaling molecules, and of transcription factors such as homeobox containing genes in different developmental phases and tissue compartments of the developing tooth germ. The function of growth factors as inductive signaling molecules in epithelial-mesenchymal interactions during early tooth development has been demonstrated by their ability to substitute for a tissue requirement in the induction of gene expression and morphologic changes in an adjacent tissue. Similarly, the importance of transcription factors such as Msx–1, Msx–2, Dlx1, Dlx2, Lef1 and Pax9 in tooth development has also been demonstrated, by elimination of the gene products using gene targeting. Mice deficient for any of these genes exhibit a severe tooth phenotype. The striking correlation of growth factor gene expression with that of transcription factors in interacting epithelial and mesenchymal tissues during organogenesis suggests a general model whereby growth factors, which can diffuse between interacting tissues, both regulate and are regulated by transcription factors. Such a model postulates recursively utilized inductive loops to account for the sequential and reciprocal signaling events that operate in organogenesis. Molecular analysis of tooth development in Msx–1 deficient mice supports the hypothesis that one function of homeobox genes is to regulate the expression of growth factors, since Msx genes function to permit inductive signaling to occur back and forth between tissue layers.
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