Epithelial Mesenchymal Interactions In Development

The contribution of epithelia-mesenchyme interaction to normal development (eg., tissue formation) and to neoplasia has become a subject of increasing interest to scientists because of recent progress in deciphering the molecular signals that mediate this interaction. Clearly, some of the same types of molecules (eg., growth factors and their receptors, proteolytic enzymes, cell adhesion molecules, and structural proteins of the extracellular matrix) mediate exchange of information between epithelia and mesenchyme during normal development and malignant growth. However, defects in the regulation of this exchange appear to contribute to malignancy by allowing growth promoting, invasogenic, and angiogenic factors to accumulate within the microenvironment of the tumor. For example, recent studies suggest that abnormal interactions between tumor epithelial cells and stromal mesenchymal cells contribute to the overproduction and accumulation of scatter factor (hepatocyte growth factor), an invasogenic and angiogenic cytokine, in certain types of tumor. The production and and activation of type IV collagenase, a matrix-degrading enzyme required for tumor cell invasion, appears to require intimate cooperation between tumor and stromal cells. The material contained in this volume highlights the state-of-the-art of knowledge of the molecular mechanisms by which epithelia and mesenchyme collaborate, and the abnormalities in these mechanisms that may lead to the development of cancer.

Craniofacial development is a multistep and intricate process initially involving a number of inductive interactions that control neural and neural crest development, which are followed by a series of epithelial-mesenchymal interactions that control outgrowth, patterning, and skeletal differentiation. Certain aspects of craniofacial development are unique developmental processes in higher vertebrates. First, in higher vertebrates the cranial neural crest, in contrast to the trunk neural crest, gives rise to the skeletal structures. These skeletal elements include those comprising mem brane bone and secondary cartilage, which with the exception of the clavicle are tissue types found exclusively in the head in higher vertebrates. Second, with the exception of the tongue, the origin of the musculature is distinct from other regions of the body. The body and tongue muscles are formed from the segmented epithelial somites whilst the head musculature is formed from unsegmented paraxial and prechordal mesoderm. Furthermore, the signalling cascades that control myogenic differentia tion appear to be distinct as determined by gene expression and the response of myogenic cells to growth factors. Finally, the neurogenic placodes, which give rise to the sensory organs and some cranial ganglia, are only found in the head. Over recent years, there have been significant advances in our knowledge of the molecular proc esses that control craniofacial development in a number of animal models. This has given insight into the genes that control many aspects of head development from the initial induction of the head to the final stages of differentiation.