TGF-beta-3 Promotes Scarless Repair of Cleft Lip in Mouse Fetuses

Abstract

TGF-β3 mediates epithelial-mesenchymal transformation during normal fusion of lip and palate, but how TGF-β3 functions during cleft lip repair remains unexplored. We hypothesize that TGF-β3 promotes fetal cleft lip repair and fusion by increasing the availability of mesenchymal 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 platelets expressing TGF-β3, 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-β3. 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-β3 regulation of mesenchymal cell proliferation and migration at the site of repair.