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The role of APCDD1 in epithelial rearrangement in tooth morphogenesis

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Abstract

Adenomatosis polyposis coli downregulated 1 (APCDD1), a negative regulator of Wnt signaling, was examined to understand detailed mechanisms underlying Wnt signaling tooth development. In situ hybridization showed that Apcdd1 was expressed in the condensed mesenchyme at the bud stage, and in the inner enamel epithelium (IEE), including enamel knot (EK) at the cap stage. In vitro organ cultivation by using Apcdd1 antisense oligodeoxynucleotides was performed at E13.5 for 2 days to define the developmental functions of APCDD1 during tooth development. Analysis of histogenesis and cellular events such as cell adhesion, proliferation, apoptosis and epithelial rearrangement after Apcdd1 knockdown showed altered morphogenesis of the tooth germ with decreased cell proliferation and altered localization of cell adhesion molecules. Actin filament staining and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) labeling of IEE cells showed that Apcdd1 knockdown enhanced epithelial rearrangement in the IEE and EK. To understand the precise signaling regulations of Apcdd1, we evaluated the altered expression patterns of signaling molecules, related with Wnt and enamel knot signalings using RT-qPCR. Tooth germs at cap stage were transplanted into the kidney capsules and were allowed to develop into calcified teeth for 3 weeks. Apcdd1 knockdown increased the number of ectopic cusps on the mesial side of the tooth. Our results suggested that APCDD1 modulates the gene expression of Wnt- and EK-related signaling molecules at the cap stage of tooth development, and is involved in tooth cusp patterning by modulating the epithelial rearrangement in the IEE.

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Acknowledgments

This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP; No. 2008–0062282).

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Authors and Affiliations

  1. Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 700-412, Korea

    Sanjiv Neupane, Wern-Joo Sohn, Gi-Jeong Gwon, Youngkyun Lee & Jae-Young Kim

  2. Department of Dental Hygiene, IHBR, Kyungpook National University, Daegu, Korea

    Ki-Rim Kim

  3. School of Life Science and Biotechnology, Kyungpook National University, Daegu, Korea

    Sanggyu Lee

  4. Department of Oral and Maxillofacial Radiology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea

    Chang-Hyeon An

  5. Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea

    Jo-Young Suh

  6. Department of Oral and Maxillofacial Pathology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea

    Hong-In Shin

  7. Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, Japan

    Hitoshi Yamamoto

  8. Division in Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea

    Sung-Won Cho

Authors
  1. Sanjiv Neupane
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  2. Wern-Joo Sohn
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  3. Gi-Jeong Gwon
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  4. Ki-Rim Kim
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  5. Sanggyu Lee
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  7. Jo-Young Suh
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  8. Hong-In Shin
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  9. Hitoshi Yamamoto
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  10. Sung-Won Cho
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  11. Youngkyun Lee
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  12. Jae-Young Kim
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Corresponding author

Correspondence to Jae-Young Kim.

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Supplementary Figure 1

Graphical presentation of buccolingual diameter (a), number of TUNEL-positive cells in the EK (b) and number of Ki67-positive cells in the IEE (c). The scheme for counting IEE cells (d). The shaded area indicates the region from which Ki67-positive cells were counted (d); **p < 0.01. EK, enamel knot; IEE, inner enamel epithelium (TIFF 4687 kb)

Supplementary Figure 2

Altered expression of Wnt signaling-related signaling molecules in tooth germ cultivated at E13 for 2 days (TIFF 769 kb)

Supplementary Figure 3

Whole-mount in situ hybridization of Fgf4 after in vitro cultivation at E15.5 for 3 days. The AS-ODN-treated specimen showing increased number of Fgf4 expression spots on the mesial and distal parts of the tooth germ compared with that in the control specimen (a, b). The arrows indicate increased Fgf4 expression. Bu, buccal; Di, distal; Li, lingual; Me, mesial. Scale bars: 200 μm (TIFF 590 kb)

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Neupane, S., Sohn, WJ., Gwon, GJ. et al. The role of APCDD1 in epithelial rearrangement in tooth morphogenesis. Histochem Cell Biol 144, 377–387 (2015). https://doi.org/10.1007/s00418-015-1345-z

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