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The role of APCDD1 in epithelial rearrangement in tooth morphogenesis

 Sanjiv Neupane  ;  Wern-Joo Sohn  ;  Gi-Jeong Gwon  ;  Ki-Rim Kim  ;  Sanggyu Lee  ;  Chang-Hyeon An  ;  Jo-Young Suh  ;  Hong-In Shin  ;  Hitoshi Yamamoto 
 HISTOCHEMISTRY AND CELL BIOLOGY, Vol.144(4) : 377-387, 2015 
Journal Title
Issue Date
Animals ; Cell Adhesion Molecules/metabolism ; Cell Proliferation ; Epithelial Cells/metabolism* ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Gestational Age ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism* ; Membrane Proteins/genetics ; Membrane Proteins/metabolism* ; Mice ; Molar/embryology ; Molar/metabolism* ; Morphogenesis ; Odontogenesis* ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/metabolism ; Tissue Culture Techniques ; Wnt Signaling Pathway
APCDD1 ; Cusp patterning ; Enamel knot ; Epithelial rearrangement ; Inner enamel epithelium
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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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Cho, Sung Won(조성원) ORCID logo https://orcid.org/0000-0001-7505-9769
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