The Role of the Wnt Signaling Pathway in Upper Jaw Development of Chick Embryo
The Role of the Wnt Signaling Pathway in Upper Jaw Development of Chick Embryo
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DOI：
10.1267/ahc.18038
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Wanaka, Akio
中科院分区：
文献类型：
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作者：
Shimomura, Tadahiro;Kawakami, Masayoshi;Wanaka, Akio
摘要唇裂合并或不合并腭裂，通常是由于鼻内侧与鼻外侧及上颌骨的融合失败所致。这种失败抑制面部形态发生调节的几个主要的形态发生信号通路。我们假设CLP是由Wnt信号通路的失败引起的。为了检查Wnt信号传导是否可以影响上颌发育，我们将浸有Dickkopf-1（Dkk-1）、Alsterpaullone（AL）或Wnt 3a的珠粒应用于鸡胚的上颌突的右侧。胚胎在治疗侧显示上颌骨缺损，骨骼染色显示前颌骨和腭骨发育不全，这是Dkk-1浸泡珠植入的结果。5-溴-2 '-脱氧尿苷（BrdU）阳性细胞数在治疗上颌突植入后24和48小时显着降低。Bmp 4、Tbx 22、Sox 9和Barx 1的表达在Dkk-1处理的上颌突中被证实下调，这表明上颌骨的畸形是由Wnt信号通路的基因靶点控制的。N-钙粘蛋白的表达在AL处理后6小时的胚胎上颌骨中被免疫组化观察到，并在24小时增加。通过AL或Wnt 3a增强的Wnt信号传导上调Msx 1、Bmp 4、Tbx 22、Sox 9和Barx 1的表达水平。我们的数据表明，Wnt信号通路通过Bmp 4，Tbx 22，Sox 9和Barx 1调节上颌骨的形态发生和生长。Wnt信号可能通过Msxl调节N-钙粘蛋白的表达，导致细胞聚集用于骨软骨形成。
Cleft lip with or without cleft palate (CLP) usually results from a failure of the medial nasal prominences to fuse with the lateral and maxillary prominences. This failure inhibits facial morphogenesis regulated by several major morphogenetic signaling pathways. We hypothesized that CLP results from the failure of the Wnt signaling pathway. To examine whether Wnt signaling can influences upper jaw development, we applied beads soaked with Dickkopf-1 (Dkk-1), Alsterpaullone (AL) or Wnt3a to the right side of the maxillary prominence of the chick embryo. The embryo showed a defect of the maxilla on the treated side, and skeletal staining revealed hypoplasia of the premaxilla and palatine bone as a result of Dkk-1-soaked bead implantation. 5-bromo-2'-deoxyuridine (BrdU)-positive cell numbers in the treated maxillary prominence were significantly lower at both 24 and 48 hr after implantation. Down-regulation of the expression of Bmp4, Tbx22, Sox9, and Barx1 was confirmed in the maxillary prominence treated with Dkk-1, which indicated that the deformity of the maxillary bone was controlled by gene targets of the Wnt signaling pathway. Expression of N-cadherin was seen immunohistochemically in the maxillary prominences of embryos at 6 hr and increased at 24 hr after AL treatment. Wnt signaling enhanced by AL or Wnt3a up-regulated the expression levels of Msx1, Bmp4, Tbx22, Sox9, and Barx1. Our data suggest that the Wnt signaling pathway regulates maxillary morphogenesis and growth through Bmp4, Tbx22, Sox9, and Barx1. Wnt signaling might regulate N-cadherin expression via Msxl, resulting in cell aggregation for osteochondrogenesis.