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Induction of palate epithelial mesenchymal transition by transforming growth factor β3 signaling
Author(s) -
Jalali Azadeh,
Zhu Xiujuan,
Liu ChangChih,
Nawshad Ali
Publication year - 2012
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2012.01364.x
Subject(s) - mesenchyme , smad , microbiology and biotechnology , biology , epithelial–mesenchymal transition , transforming growth factor , morphogenesis , transcription factor , cadherin , cell migration , secondary palate , snail , signal transduction , mesenchymal stem cell , cell , anatomy , genetics , transition (genetics) , gene , ecology
Transforming growth factor ( TGF β)3 is essential for palate development, particularly during the late phase of palatogenesis when the disintegration of the palatal medial edge seam ( MES ) occurs resulting in mesenchymal confluence. The MES is composed of medial‐edge epithelium ( MEE ) of opposite palatal shelves; its complete disintegration is essential for mediating correct craniofacial morphogenesis. This phenomenon is initiated by TGF β3 upon adherence of opposing palatal shelves, and subsequently epithelial–mesenchymal transition ( EMT ) instigates the loss of E ‐ C adherin, causing the MES to break into small epithelial islands forming confluent palatal mesenchyme; however, apoptosis and cell migration or in combination of all are other established mechanisms of seam disintegration. To investigate the molecular mechanisms that cause this E ‐ C adherin loss, we isolated and cultured murine embryonic primary MES cells from adhered palates and employed several biological approaches to explore the mechanism by which TGF β3 facilitates palatal seam disintegration. Here, we demonstrate that TGF β3 signals by activating both S mad‐dependent and S mad‐independent pathways. However, activation of the two most common EMT related transcription factors, S nail and SIP , was facilitated by S mad‐independent pathways, contrary to the commonly accepted S mad‐dependent pathway. Finally, we provide the first evidence that TGF β3‐activated S nail and SIP 1, combined with S mad4, bind to the E ‐ C adherin promoter to repress its transcription in response to TGF β3 signaling. These results suggest that TGF β3 uses multiple pathways to activate S nail and SIP 1 and these transcription factors repress the cell–cell adhesion protein, E ‐ C adherin, to induce palatal epithelial seam EMT . Manipulation and intervention of the pathways stimulated by TGF β3 during palate development may have a significant therapeutic potential.