Molecular Maternal Effect on Etiology of cleft lip nad palate in Fetal Mouse Model.

在唇腭裂的正常融合过程中，转化生长因子-β3介导了上皮-间充质转化，但转化生长因子-β3在唇裂修复过程中的作用尚不清楚。我们假设转化生长因子-b3通过增加间充质细胞的可获得性来促进胎儿唇裂的修复和融合。在这项研究中，我们证明了小鼠胚胎的唇裂可以通过胎儿手术修复，产生无疤痕的融合。在手术部位，我们首先观察到表达转化生长因子-b3的血小板的输注，随后细胞周期蛋白D1和张力蛋白-C的表达增加，并伴随着间充质细胞增殖的增加。在体外无血清培养系统中，唇裂外植体在外源转化生长因子-b3的存在下融合。培养的嘴唇细胞周期蛋白D1和Tenascin-C表达上调。这些发现表明，显微手术修复发生无疤痕融合的胎儿唇裂是通过调节修复部位的间充质细胞增殖和迁移来实现的。

TGF-b3 mediates epithelial-mesenchymal transformation during normal fusion of lip and palate, but how TGF-b3 functions during cleft lip repair remains unexplored. We hypothesize that TGF-b3 promotes fetal cleft lip repair and fusion by increasing the availability of nesenchymal cells. In this investigation, we demonstrated that cleft lips in mouse fetuses were repaired by fetal surgery, producing scarless fusion. At the site of the operation, we first observed an infusion of platelet expressing TGF-b3, followed by increased expression of cyclin D1 and tenascin-C, and coupled with increased mesenchymal cell proliferation. In an ex vivo serumless culture system, cleft lip explants fused in the presence of exogenous TGF-b3. Cultured lips also showed up-regulation in cyclin D1 and tenascin-C expression. These findings suggest that microsurgical repair of cleft lip in the fetus that produced scarless fusion is mediated by TGF-b3 regulation of mesenchymal cell proliferation and migration at the site of repair.