Molecular biology experimental strategies for craniofacial-oral-dental dysmorphology

This paper is a minireview of molecular biology experimental strategies for problems within craniofacial-oral-dental biology. Many of these strategies have already made remarkable contributions towards understanding the complex developmental processes associated with craniofacial biology. For example, the utilization of these strategies has resulted in the successful mapping of approximately 70 genes related to craniofacial anomalies (e.g., Pax, retinoic acid receptors, cadhedrins, aggrecan, cell adhesion molecules, substrate adhesion molecules, etc.), 30 genes related to dental tissue disorders (e.g., BMPs, bone morphogenetic proteins; dentin phosphoproteins, dentin sialoglycoproteins, enamelins, amelogenins), 20 genes related to facial clefting defects (e.g., Hox genes, transforming growth factor alpha), and 3 genes related to craniosynostosis (e.g., Msx-2). This minireview highlights selected examples of scientific progress derived from the following experimental strategies: (i) molecular approaches to the organization of the mouse and human chromosomes, with the mapping of specific gene sequences linked to human diseases (e.g., amelogenesis imperfecta, Boston type craniosynostosis, Rieger's syndrome, Treacher Collins syndrome); (ii) reverse genetic approaches for studies of gene function; (iii) homologous recombinations and the advances from "knock-out" transgenic mouse models for human craniofacial-oral-dental diseases; (iv) mutational analyses of congenital craniofacial-oral-dental dysmorphogenesis; (v) structural biology studies using computer-assisted molecular modeling for protein-protein, protein-nucleic acid and protein-inorganic interactions; (vi) computer modeling of genetic paradigms; and (vii) a cluster of newer methodologies including computer-assisted morphometry, new microinjection techniques, new cell membrane and intracellular dyes, and a number of new RNA and DNA viral constructs for the delivery of genes to enhance the resolution of cell fate maps, cell lineage studies and gene therapy approaches to human diseases.