MOLECULAR CONTROLS OF SECONDARY PALATE MORPHOGENESIS

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The long-term goal of this research is to examine the molecular mechanisms that control the epithelial-mesenchymal transformation of medical edge epithelial cells (MEE) during palatogenesis. Recent accomplishments in this research group have documented the fate of the medial edge epithelial cells both in vitro and in vivo. These studies have shown that rather that undergoing a pattern of programmed cell death, coincident with palatal fusion, the cells remain viable however they undergo a phenotypic change from epithelium to mesenchyme. The transdifferentiated MEE have the capacity for cell proliferation and remain in the connective tissue of the palatal mucosa. This new observation presents several unique opportunities for examining both the intracellular changes associated with MEE phenotypic transdifferentiation and the extracellular signals that may be responsible for epithelial- mesenchymal transformation. Our recent observations on the fate of the MEE during palatogenesis have led to the hypothesis that, Specific changes in gene expression are restricted to the medial edge epithelia and associated with the mechanism for epithelial-mesenchymal transformation of these cells. The specific aims used to examine this hypothesis will be; 1) to characterize the molecular phenotype of MEE during epithelial-mesenchymal transdifferentiation both in vitro and in vivo and relate these changes temporally to the morphologic processes of palatal fusion, 2) to examine the pattern of expression of genes associated with the cell cycle and the function/modification of their gene products to correlate molecular control of MEE proliferation with the process of epithelial-mesenchymal transformation, 3) to characterize the pattern of expression of cell adhesion molecules on the MEE during palatogenesis to determine the role of interaction with the mesenchymal extracellular matrix and the phenotypic changes that occur in the cells, 4) to evaluate the molecular alterations that result from the effects of a developmental morphogen/teratogen, retinoic acid, and how these effects are mediated by specific molecular receptors. These studies will contribute to a better characterization of the molecular mechanisms associated with palatal fusion and MEE transdifferentiation and provide a molecular basis for examinations of the etiology of craniofacial birth defects.