Microtubule disassembly prevents palatal fusion and alters regulation of the E-cadherin/catenin complex
Original Article | Published: 7 March 2013
Yukiko Kitase and Charles F. Shuler*
Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver BC, Canada
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-β induces EMT in medial edge epithelium (MEE) by down-regulation of an epithelial marker, E-cadherin. Microtubule disassembly impaired palatal fusion leading to a multi-layered 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-β/SMAD2 signaling pathway, which led to a failure in EMT. These results suggest that the microtubule cytoskeleton plays an important role in mediating TGF-β/SMAD2 signals to control E-cadherin gene expression in MEE during palatal fusion.