title: Microtubule disassembly prevents palatal fusion and alters regulation of the E-cadherin/catenin complex.
abstract: 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.
authors.affiliation: Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver BC, Canada.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kitase
authors.forename: Charles F
authors.initials: CF
authors.lastname: Shuler
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D009924:Organ Culture Techniques; D010159:Palate / Q000196:embryology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D015820:Cadherins; D051177:Catenins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D050257:Tubulin Modulators; D015739:Nocodazole