title: The role of APCDD1 in epithelial rearrangement in tooth morphogenesis.
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.
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 700-412, Korea.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Neupane
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 700-412, Korea.
authors.forename: Wern-Joo
authors.initials: WJ
authors.lastname: Sohn
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 700-412, Korea.
authors.forename: Gi-Jeong
authors.initials: GJ
authors.lastname: Gwon
authors.affiliation: Department of Dental Hygiene, IHBR, Kyungpook National University, Daegu, Korea.
authors.forename: Ki-Rim
authors.initials: KR
authors.lastname: Kim
authors.affiliation: School of Life Science and Biotechnology, Kyungpook National University, Daegu, Korea.
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Radiology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.
authors.forename: Chang-Hyeon
authors.initials: CH
authors.lastname: An
authors.affiliation: Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.
authors.forename: Jo-Young
authors.initials: JY
authors.lastname: Suh
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.affiliation: Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 700-412, Korea.
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 700-412, Korea. jykim91@knu.ac.kr.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005865:Gestational Age; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008963:Molar / Q000196:embryology / Q000378:metabolism*; D009024:Morphogenesis; D009805:Odontogenesis; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D060449:Wnt Signaling Pathway
chemical_list: C498341:Apcdd1 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense
keywords: APCDD1; Cusp patterning; Enamel knot; Epithelial rearrangement; Inner enamel epithelium