CP 27 GENE FUNCTION IN TOOTH DEVELOPMENT

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DESCRIPTION (Adapted from the Investigator's Abstract): The present proposal focuses on the function of a novel gene cp27 in the morphogenesis and molecular signaling that occurs during tooth development. CP27 has been recently cloned from an embryonic stage 11 mouse library and completely sequenced in the applicant's laboratory (Diekwisch et al. 1999). CP27 demonstrates highly restricted expression patterns in two distinct localizations during tooth development: (i) at the epithelial- mesenchymal interface of dental lamina stage tooth germs and (ii) in the stellate reticulum of cap stage tooth organs. The Principal Investigator's preliminary data suggest that CP27 is an extracellular matrix protein of the developing tooth organ and a critical molecular factor in normal tooth morphogenesis. The present proposal is designed (i) to determine the function of CP27 in the morphogenesis and signaling during initial tooth development, and (ii) to establish the role of CP27 in the stellate reticulum in relationship to extracellular matrix synthesis. The long-term goals of this project are to understand the regulatory role of CP27 during tooth morphogenesis through analysis of the tissue specific mechanisms of gene expression. Four specific aims are proposed to address the hypothesis that CP27 is an extracellular matrix molecule in the developing tooth organ that is critical both to the initiation of tooth morphogenesis and to the morphogenetic control of tooth crown formation. Specific Aim 1 proposes to determine the temporospatial expression and localization of CP27 in the developing tooth organ. Specific Aim 2 proposes studies to characterize the mechanism of CP27 regulating cellular proliferation and growth at the onset of tooth development. Specific Aim 3 will determine the effect of CP27 on apoptosis, anoikis, and cell fate in tooth development. Specific aim 4 proposes studies to evaluate the role of CP27 controlling cell shape and tissue architecture of the developing tooth organ. The proposed studies will determine the function of CP27 in the epithelia1-mesenchymal interactions that occur during tooth development. Understanding the function of CP27 may provide the basis for the development of novel clinical aids for craniofacial diseases.