Microtubule disassembly prevents palatal fusion and alters regulation of the E-cadherin/catenin complex

During palatal fusion, the midline epithelial seam (MES) degrades to achieve mesenchymal confluence. Epithelial mesenchymal transition (EMT) is one mechanism which is active in MES degradation. TGF-beta induces EMT in medial edge epithelium (MEE) by down-regulation of an epithelial marker, E-cadherin. Microtubule disassembly impaired palatal fusion leading to a multilayered MES in the mid-region. In this study, we investigated the effect of microtubule disruption on the regulation of the E-cadherin/catenin adhesion complex. Nocodazole (NDZ) enhanced the accumulation of the adhesion complex at cell-cell contacts in MEE, while loss of the adhesion complex was observed in the control. NDZ caused aberrant regulation of the E-cadherin transcriptional repressors (Snail and Zeb) and the activator (c-MYC) through inhibition of the TGF-beta/SMAD2 signaling pathway, which led to a failure in EMT.These results suggest that the microtubule cytoskeleton plays an important role in mediating TGF-beta/SMAD2 signals to control E-cadherin gene expression in MEE during palatal fusion.