The epithelial disintegration and the mesenchymal bridging are critical steps in the fusion of facial prominences during the upper lip development. These processes of epithelial-mesenchymal transition and programmed cell death are mainly influenced by Wnt signals. Axis inhibition protein2 (Axin2), a major component of the Wnt pathway, has been reported to be involved in lip development and cleft pathogenesis. We wanted to study the involvement of Axin2 in the lip development, especially during the epithelial disintegration of facial prominences. Our results show that Axin2 was expressed mainly in the epithelium of facial prominences and decreased when the prominences were about to contact each other between Hamburger-Hamilton stages 27 and 28 of chicken embryos. The epithelial integrity was destructed or kept intact by the local gain or loss of Axin2 expression, resulting in morphological changes in the facial processes and their skeletal derivatives including the maxilla, nasal, premaxilla bone, and their junctions without cleft formation. These changes were related to expression changes in nuclear β-catenin, pGSK3β, Slug, Smad3, E-cadherin, and p63. All these data indicate that Axin2 participates in the regulation of epithelial integrity and fusion by promoting epithelial disassociation, basement membrane breakdown, and seam loss during the fusion of facial prominences in lip development.

中文翻译：

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Axin2的过表达促进禽唇发育过程中面部突起的早期上皮崩解和融合。

上皮发育过程中，上皮崩解和间质桥接是融合面部突出的关键步骤。这些上皮-间质转化和程序性细胞死亡的过程主要受Wnt信号影响。据报道，轴抑制蛋白2（Axin2）是Wnt途径的主要组成部分，与唇的发育和left裂的发病机理有关。我们想研究Axin2在嘴唇发育中的参与，尤其是在面部突出的上皮崩解过程中。我们的结果表明Axin2在鸡胚的汉堡-汉密尔顿阶段27和28之间，突起主要在面部突起的上皮中表达，而突起将在彼此接触时下降。Axin2的局部增减会破坏或保持上皮的完整性表达，导致面部过程及其骨骼衍生物（包括上颌骨，鼻梁，前颌骨骨及其连接处无裂痕）的形态变化。这些变化与核β-catenin，pGSK3β，Slug，Smad3，E-cadherin和p63的表达变化有关。所有这些数据表明，Axin2通过促进上唇在唇部发育融合过程中的上皮分离，基底膜破裂和缝隙丢失而参与上皮完整性和融合的调节。