Mandibular abnormalities are a common finding in craniofacial disorders. Patterning of first branchial arch development is the result of a complex series of reciprocal epithelial-mesenchymal interactions. The epithelium establishes the pattern of odontogenesis within the first arch by inductive interaction with first arch mesenchyme. The exact nature of the inductive signal is not known. Retinoids (retinoic acid and retinol) affect craniofacial development. This effect is dose, developmental stage, and duration dependent. While exposure to retinoids can cause deficient craniofacial primordial development, they also alter patterning of odontogenesis as seen in agenesis, fusion, and supernumerary tooth bud formation. However, in these reports, the exact developmental staging and individual embryonic exposure to retinoids is not clear. In addition, the mechanism of retinoid action in first arch development is not known. Studies of embryonic palatal development indicate a relationship between retinoids and EGF receptor expression and binding affinity. This relationship in odontogenesis is only briefly described for molar tooth buds after day 12 in mouse embryos. the purpose of this project is to explore the role of retinoids and he family of EGF growth factors in patterning of first arch development in mice during the period of epithelial induction of mesenchyme ( day 8-13). Morphologic effects will be monitored in organ culture and examined by light and electron microscopy. EGF receptor expression and binding will also be studied. The effects the molecular level that will be explored are the spatial and temporal distribution of mRNA for cellular and nuclear retinoid binding proteins and mRNA for EGF and TGF alpha precursors using in situ and cytoplasmic dot blot hybridization techniques.
