Twistl function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development

Twist I is a bHLH transcription factor that regulates cell proliferation, migration, and differentiation in embryonic progenitor cell populations and transformed tumor cells. While much is known about Twistl's function in a variety of mesenchymal cell types, the role of Twistl in endocardial cushion cells is unknown. Twistl gain and loss of function experiments were performed in primary chicken endocardial cushion cells in order to elucidate its role in endocardial cushion development. These studies indicate that Twistl can induce endocardial cushion cell proliferation as well as promote endocardial cushion cell migration. Furthermore, Twistl is subject to BMP regulation and can induce expression of cell migration marker genes including Periostin, Cadherin 11, and Mmp2 while repressing markers of valve cell differentiation including Aggrecan. Previously, Tbx20 has been implicated in endocardial cushion cell proliferation and differentiation, and in the current study, Tbx20 also promotes cushion cell migration. Twistl can induce Tbx20 expression, while Tbx20 does not affect Twist] expression. Taken together, these data indicate a role for Twist] upstream of Tbx20 in promoting cell proliferation and migration and repressing differentiation in endocardial cushion cells during embryonic development. (C) 2008 Elsevier Inc. All rights reserved.