Abstract-Recent work has demonstrated the importance of the epicardium in the development of the heart. During embryogenesis, these epithelial cells provide the progenitors for the epicardium, coronary smooth muscle, endothelium, and cardiac fibroblasts. The epicardium sends important signals to the developing myocardium. Still, analysis of these epithelial cells has lagged behind that of other cardiac cell types largely because of the lack of a defined experimental cell system in which epicardial cell differentiation can be studied. The present report examines the developmental potential of a cell line derived from rat epicardial mesothelial cells. These analyses demonstrate that the cell line retains many characteristics of the intact epithelium, including the ability to form a polarized epithelium and express many epicardial genes. Our data show for the first time that these cells retain the ability to produce mesenchyme in response to specific growth factors and, importantly, to generate smooth muscle cells. Thus, this study provides evidence that these cells can serve as an important model system for the analysis of the cellular and molecular mechanisms that govern epicardial development and function.
Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. This interaction represents the first identification of any protein that has a direct physical interaction with any member of the Popdc family. Bves and GEFT are shown to colocalize in adult skeletal muscle. We also demonstrate that exogenous expression of Bves reduces Rac1 and Cdc42 activity levels while not affecting levels of active RhoA. Consistent with a repression of Rac1 and Cdc42 activity, we show changes in speed of cell locomotion and cell roundness also result from exogenous expression of Bves. Modulation of Rho-family GTPase signaling by Bves would be highly consistent with previously described phenotypes occurring upon disruption of Bves function in a wide variety of model systems. Therefore, we propose Bves as a novel regulator of the Rac1 and Cdc42 signaling cascades.Popdc ͉ cell motility ͉ GEF
It is readily apparent that the process of heart development is an intricate one, in which cells derived from many embryonic sources coalesce and coordinate their behaviors and development, resulting in the mature heart. The behaviors and mechanisms of this process are complex, and still incompletely understood. However, it is readily apparent that communication between diverse cell types must be involved in this process. The signaling that emanates from epicardial and endocardial sources is the focus of this review. KeywordsEndocardium; Epicardium; FGF; Retinoic acid; Neuregulin-1 Epicardial and endocardial signaling during cardiac developmentExquisite control and regulation is required for development of a properly functioning heart. As the heart progresses from mesoderm to a simple tube to a complex four-chambered structure, each step along this progression requires precise regulation of cellular behavior by a variety of sources. The hypoblast [1,2], epiblast [3], endoderm [4], neural tissue [5][6][7][8], endocardium [9][10][11][12][13], and epicardium [9,10,14] all signal to developing/mature muscle or cells that are fated to become myocardium during development. Additionally, the developing/mature myocardium emits signals to several of these structures (as well as to itself) that are necessary for proper development and maintenance of the cardiovascular system [15][16][17][18][19]. The proper transmittal of these signals is dependent on cellular emission of signals, cellular response to these signals, and morphogenetic movements of the organ and embryo that manipulate these communicating cells into the proper position for this communication to occur. Our focus here is to review signaling from the epicardium and endocardium, focusing on events that occur during embryonic development. Embryonic origins of the endocardium, epicardium, and myocardiumWhile a thorough discussion of the early embryonic development of the components of the mature heart is not within the scope of this review, a brief review of the embryonic origins and mechanisms that give rise to these tissues is useful for this discussion. Numerous excellent and more exhaustive reviews of endocardial [20][21][22][23][24], epicardial [25][26][27][28][29], and myocardial [30][31][32] [33][34][35]. These cells coalesce to form the cardiac crescent, which then fuses to become the primitive heart tube [36]. The rhythmically contracting primitive heart tube at this point consists of a tube of epithelial endocardium surrounded by an epithelial tube of myocardium, and a layer of cardiac jelly separates these two tubes. This tube displays polarity along the anterior-posterior axis, as gene products expressed at this stage demonstrate that some early cell fate decisions have been made [36][37][38]. The linear heart tube then begins the process of looping, which establishes the position of the future chambers of the heart. Through this process, the presumptive atria are positioned anterior to the portion of the heart tube that gives rise to the ventr...
Bves (blood vessel/epicardial substance) is a transmembrane protein postulated to play a role in cell-cell interaction/adhesion. It was independently isolated by two groups as a gene product highly enriched in the developing heart. Disagreement exists about its expression during development. Most notably, the expression of Bves in non-muscle cells is disputed. Determining the expression profile of Bves is a critical initial step preceding the characterization of protein function in development and in the adult. We have generated new monoclonal antibodies against mouse Bves and used these immunoreagents to elucidate Bves expression in development. As expected, we detect Bves in myocytes of the developing heart throughout development. In addition, skeletal and smooth muscle cells including those of the coronary system express Bves. Finally, specific, but not all, epithelial derivatives of the three germ layers are stained positively with these monoclonal antibodies. Protein expression in cultured epithelial and muscle cell lines corroborate our in vivo findings. Taken together, these results demonstrate the expression of Bves in a wide range of epithelial and muscle cells during mouse embryogenesis and indicate a broad function for this protein in development, and show that these newly generated reagents will be invaluable in further investigation of Bves.
Bves was discovered through subtractive screens designed to identify heart-enriched transcripts. Bves is a transmembrane protein that possesses a highly conserved structure among species of the animal kingdom.
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