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ROCK1 Expression is Regulated by TGFβ3 and ALK2 During Valvuloseptal Endocardial Cushion Formation
Author(s) -
Sakabe Masahide,
Sakata Hirokazu,
Matsui Hiroko,
Ikeda Kazuo,
Yamagishi Toshiyuki,
Nakajima Yuji
Publication year - 2008
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.20708
Subject(s) - rock1 , endocardium , microbiology and biotechnology , noggin , mesenchyme , mesenchymal stem cell , bone morphogenetic protein , biology , transforming growth factor , chemistry , medicine , kinase , protein kinase a , biochemistry , gene
Abstract During early heart development at the looped heart stage, endothelial cells in the outflow tract and atrioventricular (AV) regions transform into mesenchyme to generate endocardial cushion tissue. This endocardial epithelial–mesenchymal transition (EMT) is regulated by several regulatory pathways, including the transforming growth factor‐beta (TGFβ), bone morphogenetic protein (BMP), and Rho‐ROCK pathways. Here, we investigated the spatiotemporal expression pattern of ROCK1 mRNA during EMT in chick and examined whether TGFβ or BMP could induce the expression of ROCK1. At the onset of EMT, ROCK1 expression was up‐regulated in endothelial/mesenchymal cells. A three‐dimensional collagen gel assay was used to examine the mechanisms regulating the expression of ROCK1. In AV endocardium co‐cultured with associated myocardium, ROCK1 expression was inhibited by either anti‐TGFβ3 antibody, anti‐ALK2 antibody or noggin, but not SB431542 (ALK5 inhibitor). In cultured preactivated AV endocardium, TGFβ3 protein induced the expression of ROCK1, but BMP did not. AV endothelial cells that were cultured in medium supplemented with TGFβ3 plus anti‐ALK2 antibody failed to express ROCK1. These results suggest that the expression of ROCK1 is up‐regulated at the onset of EMT and that signaling mediated by TGFβ3/ALK2 together with BMP is involved in the expression of ROCK1. Anat Rec, 291:845‐857, 2008. © 2008 Wiley‐Liss, Inc.