After the genome wide screening, a molar tooth forming gene, Apcdd1 (Adenomatosis polyposis coli down-regulated 1), was selected and evaluated expression pattern in mice tooth development using RT-qPCR and in situ hybridizations. At E13.5 distinctive expression pattern of Apcdd1 was detected in condensed mesenchyme and at E14.5, Apcdd1 was observed in the enamel knot (EK). In vitro organ cultivation using Apcdd1 antisense oliodeoxynucleotides (AS-ODN) was employed at E13 for 2 days to define the developmental function of Apcdd1. After knocking down of Apcdd1, histogenesis and cellular events such as cell adhesion, proliferation and apoptosis, were examined. These results showed the altered morphogenesis of tooth germ with lower cell proliferation and changed localization patterns of cell adhesion molecules after the Apcdd1 knocking down. Epithelial rearrangement was also affected by Apcdd1 knocking down. Further, we evaluated altered expression patterns of signaling molecules, related with EK, using RT-qPCR to understand the precise signaling regulations of Apcdd1. In addition, renal transplantation was employed to understand the detailed developmental function of Apcdd1 at cap stage in tooth crown formation. Overall, we suggest that Apcdd1 would play crucial roles at cap stage in tooth development.
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