Colorectal Cancer Genes are Involved in Tooth Development

Objectives: It has been suggested that tooth agenesis and colorectal cancer (CRC) may have a common genetic etiology. Using an unbiased gene-discovery approach, we recently found strong association between the genome-wide associated CRC genes ATF1 and DUSP10 and tooth agenesis. However, expression of these genes/proteins has not yet been described during tooth development. Our aim is to investigate the spatiotemporal expression pattern of the ATF1 and DUSP10 during murine tooth development.
Methods: Mouse head tissue sections at embryonic days (E) 12.5, 14.5, 15.5, 16.5, 18.5, and at birth (P0) were used in immunofluorescence and immunohistochemistry procedures for ATF1 and DUSP10, respectively. Primary antibodies (rabbit anti-mouse ATF1 and rabbit anti-mouse DUSP10), and secondary antibodies [goat anti-rabbit-Alexa 555 (ATF1), and biotynilated horse anti-rabbit IgG with Novared peroxidase substrate kit (DUPS10)] were used to detect the localization of these proteins in mouse teeth. Counterstaining was performed using DAPI or Mayers’ hematoxylin. Imaging was performed using Nikon Eclipse E400 microscope.

Results: ATF1 and DUSP10 were expressed throughout tooth development. ATF1 was detected at E12.5 in the condensating ectomesenchymal cells below the placode. At E14.5, ATF1 was expressed in the inner epithelium and stratum intermedium of the enamel organ, and in a few dental papilla cells. Later, expression concentrated in the stratum intermedium, then in secretory ameloblasts by P0. DUSP10 was expressed in the proliferating dental lamina, surrounded by underlying ectomesenchymal cells at E12.5. At E14.5, expression was detected on the enamel organ and dental papilla cells, and in dental follicle by E16.5. At 18.5, DUSP10 was found in enamel organ, ectomesenchymal cells of the dental papilla and dental follicle cells. At P0, strong expression was observed in preameloblasts and the underlying odontoblast layer.
Conclusions: Our results reveal ATF1 and DUSP10 as novel players involved in tooth development in mice and humans.