Tooth development is a complex schedule of cell division, differentiation, morphogenesis and tissue-specific extracellular matrix biomineralization. The major objective of this research project is to determine if locally produced growth factors, acting as autocrine and/or paracrine mediators, regulate dentine and enamel biomineralization. We propose to test the hypothesis that time and position-restricted growth factor expression regulates dentine and enamel biomineralization. A recently developed simple organ culture system devoid of exogenous serum or plasma supplementation provides a controlled model to test our hypothesis. The following specific aims are designed to test our hypothesis: (i) to identify and quantitate locally produced growth factor mRNAs and translation products during dental tissue biomineralization; (ii) to determine the timing and position of selected growth factor expression; (iii) to determine if selected exogenous growth factors down-regulate local transcription of growth factors; (iv) to determine if endocrine hormones (e.g. growth hormone) up-regulate locally produced growth factors and stimulate biomineralization; and (v) to determine the function(s) of selected growth factors in dentine and enamel biomineralization. Methods employed include microdissection of embryonic mouse molar tooth organs, organ culture using serumless and chemically-defined medium, mRNA phenotyping using RT-PCT, in situ hybridization, immunocytochemistry, microinjection, immunoperturbation and antisense assays, light and electron microscopy, electron diffraction assays, and computer-assisted three- dimensional reconstruction. These studies use embryonic, fetal and neonatal Swiss Webster strain mouse molar tooth organs.
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