Regulation of organogenesis. Common molecular mechanisms regulating the development of teeth and other organs.

Abstract

Vertebrate organs develop from epithelial and mesenchymal tissues, and during their early development they share common morphological features. These include condensation of the mesenchymal cells and thickening, folding or branching of epithelial sheets. Sequential and reciprocal interactions between the epithelial and mesenchymal tissues play central roles in regulation of the morphogenesis of all organs. During recent years increasing amounts of molecular data have accumulated from studies describing developmental changes in expression patterns of molecules, as well as from functional in vitro studies and from the generation of transgenic mice. In this review article, we discuss common features in the molecular regulation that appear to be shared by the developing tooth and other organs. Several growth factors have been shown to act as inductive signals mediating epithelial-mesenchymal interactions in different organs. The early signals are proposed to regulate the expression of master regulatory genes, such as transcription factors. In early tooth germ, bone morphogenetic proteins BMP-2 and BMP-4 regulate expression of the homeobox containing genes Msx-1 and Msx-2. These may specify early patterning of organs through regulation of molecules at the cell surface and the extracellular matrix, such as syndecan-1 and tenascin. Changes in cell adhesion and matrix remodelling, particularly in the organ-specific mesenchyme and in basement membrane contribute to formation of mesenchymal cell condensations and to epithelial morphogenesis. Several growth factors and their receptors, particularly in the TGF beta-, FGF- and EGF- families, have been implicated in formation of mesenchymal condensates and in epithelial morphogenesis of many organs, including the tooth. It is apparent that molecules which regulate morphogenesis in different organs are potential candidate genes for congenital malformation syndromes in which several organs are affected.