The development of the face requires a complex series of interactions between the epithelium and the mesenchyme. The different sets of instructive interactions result in patterning of the facial primordia directly linked to both the development of specific craniofacial structures and the fate of specific cells. Secondary palatal development has 3 specific patterning stages, the growth zone phase, dorsal-ventral patterning of the medial edge epithelium in the midline and the anterior-posterior patterning of the palatal shelf. The MEE are dorsal-ventral patterned such that some cells migrate to the oral or nasal surfaces while others undergo epithelial-mesenchymal transdifferentiation. The cell fate of the MEE is established in a dorsal-ventral orientation and regulation of these fates is highly controlled. Anterior-posterior patterning of the palatal shelves regulates timing of palatal fusion and exhibits spatially distinct regulation of the fusion events. The growth zone, dorsal-ventral and anterior-posterior patterning of the palatal shelves are regulated locally by specific inductive signals. TGF-B3 has been shown to be 1 critical signaling molecule regulating the fate of the MEE during palatogenesis and has led to the hypothesis that; Medial edge epithelial cell differentiation is controlled by autocrine and paracrine mechanisms that establish growth zone, dorsal-ventral and anterior-posterior patterning during palatogenesis. This hypothesis will be tested with 3 specific aims; 1.To determine the factors that regulate MEE differentiation during the growth zone phase of palatogenesis and their relationship to the EGF signaling pathway in these cells; 2.To characterize the dorsal-ventral patterning of the MEE during the fusion of the palatal shelves as defined by cell adhesion molecules and growth factor receptors that determine the specific fates of different populations of MEE; 3) To examine the anterior-posterior patterning of the MEE that defines the different potentials for completion of fusion in the Smad 2 overexpression rescue of the TGF-B3 null mutant. Identification of molecular mechanisms essential to the process of palatal fusion will result in future applications to develop prenatal diagnosis strategies and specific interventions to reduce the incidence of human craniofacial birth defects. ? ?
