title: Twist regulates cadherin-mediated differentiation and fusion of human trophoblastic cells.
abstract: BACKGROUND
  The formation of the multinucleated syncytiotrophoblast of the human placenta by the terminal differentiation and fusion of mononucleate cytotrophoblasts is a critical step in pregnancy. Previous studies have demonstrated that this cellular event is dependent on a progressive decrease in the levels of the cell-adhesion molecule, E-cadherin.
  
  
  OBJECTIVE
  The aim of the study was to examine the role of Twist, a transcription factor identified as a key repressor of E-cadherin expression, in the differentiation of human trophoblastic cells.
  
  
  METHODS
  The expression of Twist or E-cadherin were first examined in first-trimester chorionic villi by immunohistochemistry. Gain- or loss-of-function studies on Twist were then performed in BeWo choriocarcinoma cells. The presence or absence of multinucleated syncytium was confirmed by indirect immunofluorescence using antibodies directed against Twist, E-cadherin, or desmoplakin, a cellular marker of mononucleate cytotrophoblasts.
  
  
  RESULTS
  The formation of multinucleated syncytium was associated with increased Twist and a decreased E-cadherin expression. Similarly, exogenous expression of Twist resulted in a continuous and progressive decrease in E-cadherin expression and the subsequent formation of syncytium in BeWo cells maintained under normal culture conditions. In contrast, small interfering RNA specific for Twist inhibited 8-Br-cAMP (8-bromoadenosine 3',5'-cyclic monophosphate)-mediated differentiation and fusion of over time in culture.
  
  
  CONCLUSIONS
  Twist is an upstream regulator of the E-cadherin-mediated terminal differentiation and fusion in a human trophoblastic cell line in vitro.
authors: Department of Obstetrics and Gynecology, University of British Columbia, 4490 Oak Street, Vancouver, British Columbia, Canada V6H 3V5.
authors: York Hunt
authors: YH
authors: Ng
authors: Hua
authors: H
authors: Zhu
authors: Peter C K
authors: PC
authors: Leung
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism; D051180:Desmoplakins / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051180:Desmoplakins; D051879:Twist-Related Protein 1; D015124:8-Bromo Cyclic Adenosine Monophosphate