Identification of genes involved in tooth development by differential microarray gene
expression. F. Li1, T.J. Pemberton1, G.A. Mendoza1, Y. Hsu1, M.L. Snead2, R. Mehrian-Shai1, P.I.
Patel1,2. 1) Institute for Genetic Medicine, University of Southern California, Los Angeles, CA; 2)
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA.
Anomalies involving tooth number, such as hypodontia or supernumerary teeth, anomalies of
tooth shape and size, and defects involving mineralization are common developmental dental
abnormalities. Positional cloning approaches and knock-out mice have identified a number of
genes critical in tooth development. As an alternative approach to identifying novel genes in
the process, we have used the Affymetrix MGE 430 2.0 microarray to examine gene expression
within developing mouse molar teeth between post-natal days 1 to 10. Analysis of the top-100
genes identified as up-regulated in the tooth RNA when compared with 16 control tissues
found that they were enriched for membrane-associated, structural, and nuclear genes, and
that the protein product of 16% is present in the extracellular matrix. Their functions were
greatly enriched for integrin binding, extracellular matrix structural components conferring
compression resistance and tensile strength, and for genes involved in biomineral formation,
tissue remodelling, skeletal development, osteoblast differentiation, organ morphogenesis, and
signal transduction regulation. Twenty-four of these genes have been previously reported to be
involved in tooth development, mutations within which are known to cause the tooth
developmental anomalies amelogenesis imperfecta, dentinogenesis imperfecta, and
trichodentoosseous syndrome. Sixteen genes of unknown function were also identified. RTQPCR has confirmed the up-regulation of 25 of these genes within the tooth RNA. However,
further work is required to confirm the localization of expression within the developing tooth
and to determine their role in tooth development. We conclude that microarray and RT-QPCR
expression analyses of the developing tooth can facilitate the identification of novel genes
involved in the process, which can aid future candidate gene selection during the investigation