The role of APCDD1 in epithelial rearrangement in tooth morphogenesis
The role of APCDD1 in epithelial rearrangement in tooth morphogenesis
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DOI：
10.1007/s00418-015-1345-z
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发表时间：
2015-07
影响因子：
2.3
通讯作者：
Sanjiv Neupane;Wern-Joo Sohn;Gi-Jeong Gwon;Kirim Kim;Sanggyu Lee;Chang-Hyeon An;Jo-Young Suh;Hong-In Shin;Hitoshi Yamamoto;Sung-Won Cho;Youngkyun Lee;Jae-Young Kim
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文献类型：
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作者：
Sanjiv Neupane;Wern-Joo Sohn;Gi-Jeong Gwon;Kirim Kim;Sanggyu Lee;Chang-Hyeon An;Jo-Young Suh;Hong-In Shin;Hitoshi Yamamoto;Sung-Won Cho;Youngkyun Lee;Jae-Young Kim
研究人员检测了Wnt信号的负调节因子——大肠息肉腺瘤病下调1 (APCDD1)，以了解Wnt信号牙齿发育的详细机制。原位杂交表明，apcdd1在芽期的凝聚间质中表达，在帽期的内牙釉质上皮（IEE），包括牙釉质结（EK）中表达。应用APCDD1反义寡脱氧核苷酸体外器官培养，在E13.5条件下培养2天，以确定APCDD1在牙齿发育过程中的发育功能。apcdd1敲低后的组织发生和细胞事件（如细胞粘附、增殖、凋亡和上皮重排）分析显示，牙胚形态发生改变，细胞增殖减少，细胞粘附分子定位改变。肌动蛋白丝染色和1,1 ' -二十八烷基-3,3,3 ',3 ' -四甲基多高氯酸碳菁（DiI）标记显示，apcdd1敲低可增强IEE和EK的上皮重排。为了了解Apcdd1的确切信号调控，我们使用RT-qPCR方法评估了与Wnt和珐琅质结信号相关的信号分子表达模式的改变。将牙帽期的牙胚移植到肾囊内，使其发育为钙化牙3周。apcdd1基因敲除增加了牙齿内侧异位尖的数量。我们的研究结果表明，APCDD1在牙齿发育的帽期调节Wnt-和ek相关信号分子的基因表达，并通过调节IEE中上皮重排参与牙尖图案的形成。
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 thatApcdd1was 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 usingApcdd1antisense 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 afterApcdd1knockdown 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 thatApcdd1knockdown 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.Apcdd1knockdown 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.