Expression of new genes in vertebrate tooth development and p63 signaling.

BACKGROUND:p63 is an evolutionarily ancient transcription factor essential to vertebrate tooth development. Our recent gene expression screen comparing wild-type and "toothless" p63^-/- mouse embryos implicated in tooth development several new genes that we hypothesized act downstream of p63 in dental epithelium, where p63 is also expressed. RESULTS:Via in situ hybridization and immunohistochemistry, we probed mouse embryos (embryonic days 10.5-14.5) and spotted gar fish embryos (14 days postfertilization) for these newly linked genes, Cbln1, Cldn23, Fermt1, Krt15, Pltp and Prss8, which were expressed in mouse and gar dental epithelium. Loss of p63 altered expression levels but not domains. Expression was comparable between murine upper and lower tooth organs, implying conserved gene functions in maxillary and mandibular dentitions. Our meta-analysis of gene expression databases supported that these genes act within a p63-driven gene regulatory network important to tooth development in mammals and more evolutionary ancient vertebrates (fish, amphibians). CONCLUSIONS:Cbln1, Cldn23, Fermt1, Krt15, Pltp, and Prss8 were expressed in mouse and fish dental epithelium at placode, bud, and/or cap stages. We theorize that these genes participate in cell-cell adhesion, cell polarity, and extracellular matrix signaling to support dental epithelium integrity, folding, and epithelial-mesenchymal cross talk during tooth development.

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