Cleft palate is a good model to pushing us toward a deeper understanding of the molecular mechanisms of spatiotemporal patterns in tissues and organisms because of the multiple-step processes such as elevation and fusion. Previous studies have shown that the epithelial β-catenin is crucial for palatal fusion, however, the function of the mesenchymal β-catenin remains elusive. We investigate the role of mesenchymal β-catenin in palatal development by generating a β-catenin conditional knockout mouse (CKO) (Sox9CreER; Ctnnb1^F/F). We found that the CKO mice exhibited delayed palatal elevation, leading to cleft palate in both in vivo and ex vivo. Abnormal cell proliferation and repressed mesenchymal canonical Wnt signaling were found in the CKO palate. Interestingly, Filamentous actin (F-actin) polymerization was significantly reduced in the palatal mesenchyme of mutant embryos. Furthermore, overexpression of adenovirus-mediated transfection with Acta1 in the mutant could help to elevate the palatal shelves but could not prevent cleft palate in ex vivo. Our results suggest that conditionally knock out β-catenin in the palatal mesenchyme by Sox9CreER leading to delayed palatal elevation, which results in repressed mesenchymal canonical Wnt signaling, decreased cell proliferation, and reduced actin polymerization, finally causes cleft palate.

中文翻译：

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Sox9CreER 介导的腭间质中 β-连环蛋白的缺失导致腭抬高延迟，伴随着典型 Wnt 信号的抑制和肌动蛋白聚合减少

腭裂是一个很好的模型，可以推动我们更深入地了解组织和生物体中时空模式的分子机制，因为它具有多个步骤，例如抬高和融合。先前的研究表明，上皮β-连环蛋白对腭融合至关重要，然而，间充质β-连环蛋白的功能仍然难以捉摸。我们通过生成 β-连环蛋白条件性敲除小鼠 (CKO) ( Sox9 CreER; Ctnnb1 ^{F/F ) 研究间充质 β-连环蛋白在腭发育中的作用}）。我们发现 CKO 小鼠表现出延迟的上颚抬高，导致体内和体外的腭裂。在 CKO 上颚中发现异常细胞增殖和抑制间充质经典 Wnt 信号传导。有趣的是，突变胚胎的腭间充质中的丝状肌动蛋白（F-肌动蛋白）聚合显着降低。此外，在突变体中过表达腺病毒介导的 Acta1 转染可能有助于提升腭架，但不能在体外预防腭裂。我们的结果表明， Sox9有条件地敲除腭间充质中的 β-连环蛋白CreER 导致腭抬高延迟，从而导致间充质经典 Wnt 信号传导受到抑制、细胞增殖减少和肌动蛋白聚合减少，最终导致腭裂。