Antisense oligonucleotides: an experimental strategy to advance a causal analysis of development

Abstract

A variety of modified and unmodified oligonucleotides (ODNs) have been examined as antisense inhibitors of gene expression. Of particular interest has been the application of antisense inhibitory experimental strategies to advance a suggested causal relationship between signal transduction and inductive epithelial-mesenchymal interactions during mandibular morphogenesis, early tooth development, tooth enamel formation, lung branching morphogenesis, kidney, muscle and heart development. Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and a number of transforming growth factor beta (TGF-beta) isotype mediated signal transductions have been demonstrated to regulate inductive processes associated with significant processes in development including mouse molar tooth morphogenesis. Antisense strategies have also been useful in studies designed to associate a specific morphogen signal with homeobox (HOX) gene regulation in several embryonal carcinoma cell lines. The application and results from a number of antisense inhibitory strategies serve to support the utility of this experimental paradigm for future investigations of tooth development. This review discusses the experimental strategy, a number of technical issues and the rationale for future investigations of tooth development.