| Summary: | Cadherin gene family members are known to be involved in the differentiation of cytotrophoblasts of the human placenta. In particular, the regulation of cadherin expression is coupled with the development of an invasive phenotype and the formation of the multinucleated syncytiotrophoblast. To investigate further the mechanisms underlying the differential regulation of cadherins during these developmental processes, we have examined the role of the transcription factor known as Twist. Twist is a basic HLH (helix-loop-helix) factor which has been shown to regulate cadherin expression in a variety of human tissues under normal and pathological conditions. Using an siRNA strategy, I have determined that Twist regulates both E-cadherin and N-cadherin in distinct subtypes of human trophoblastic cells in vitro. In particular, suppression of Twist gene expression in poorly invasive BeWo choriocarcinoma cells by using Twist-specific siRNA resulted in a concomitant increase in E-cadherin mRNA and protein levels in these cells. In contrast, transfection of highly invasive extravillous cytotrophoblasts with Twist siRNA decreased N-cadherin mRNA levels in a concentration-dependent manner. Taken together, these observations indicate that Twist differentially regulates E-cadherin and N-cadherin in human trophoblastic cells, two cadherin subtypes that govern the differentiation of these cells along the non-invasive and invasive pathways respectively. Although, the results of my studies do not directly demonstrate this biological function of Twist, they support the speculation that alterations in Twist expression levels will result in cadherin-mediated disorders of pregnancy associated with aberrant trophoblast differentiation.
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