The objective of this research project is to understand at the morphological, cellular, and biochemical levels various aspects of normal and abnormal embryonic development, especially relating to craniofacial development. Retinoids are craniofacial teratogens in the human, and our results using mouse whole embryo culture demonstrate that they exert a direct effect on the embryo. Studies with neural crest cells indicate that this may be the target cell type for retinoid-induced craniofacial anomalies. Growth and differentiation of secondary palatal epithelial cells in culture are dependent upon epidermal growth factor (EGF) and a fibronectin-rich extracellular matrix (ECM) substrate. Cyclic AMP greatly enhances the EGF effect and transforming growth factor Alpha (TGFAlpha) substitutes for EGF with the palatal epithelial cells in culture. These observations reinforce our hypothesis that TGFAlpha is an important growth factor during development. Retinoic acid influences the growth and differentiation of palatal epithelial and mesenchymal cells from the mouse as well as the human embryo. Retinoid treatment decreases proliferation of palatal mesenchymal cells and results in specific changes in protein synthesis. Retinoids, along with EGF, also modulate the growth and differentiation of palatal epithelial cells in cell and organ culture.
