Biomedical subjects

Megan E Osler

Publications and source records attributed to Megan E Osler.

5 recordsLinked to original sources

PubMed2006

Xbves is a regulator of epithelial movement during early Xenopus laevis development.

Bves/pop1a is a unique, highly conserved integral membrane protein expressed in embryonic epithelia and striated muscle. Although studies have proposed a role in epithelial morphogenesis, the function of Bves/pop1a in development is completely unknown. Here we show that Xenopus laevis Bves (Xbves) RNA and protein are expressed in epithelia of the early embryo. Transfection of Xbves into nonadherent mouse L cells confers cell/cell adhesion. Global inhibition of Xbves function by morpholino injection into two-cell embryos arrests development at gastrulation by deregulating the epithelial movements of epiboly and involution. Clonal inhibition of Xbves activity within the A1 blastomere and its derivatives completely randomizes movement of its progeny within otherwise normally differentiating embryos. These data demonstrate that Bves/pop1a proteins play a critical role in epithelial morphogenesis and, specifically, in the cell movements essential for epithelial rearrangements that occur during X. laevis development.

Amino Acid Sequence↗

PubMed2006

Bves, a member of the Popeye domain-containing gene family.

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. Various approaches have been used to elucidate the expression pattern of Bves mRNA and protein as well as its function in developing and mature organisms. Emerging evidence indicates that this protein is present in muscle and epithelia of developing embryos and the adult. In vitro functional studies predict a role in cell-cell interaction and/or adhesion. In vivo analysis of protein function is very limited at present, but recent work in Xenopus supports the importance of Bves in epithelial integrity. Presented in this review is a compilation of published findings concerning Bves gene and protein characteristics, expression patterns in embryos and cells, and functional significance as determined thus far. Presently, the literature supports a hypothesis that Bves is essential to the junctional architecture of muscle and epithelial cell types. Although there remain aspects of Bves structure, expression, and function that are not completely resolved, now is an appropriate time to summarize current knowledge about this protein, the remaining questions, and what its potential role in development might be. This review will serve as a departure point for others who become interested in the study of this highly conserved protein.

Amino Acid Sequence↗

PubMed2005

Bves modulates epithelial integrity through an interaction at the tight junction.

We first identified Bves (blood vessel/epicardial substance) as a transmembrane protein that localized to the lateral compartment of the epithelial epicardium. Bves traffics to sites of cell-cell contact in cultured epicardial cells and promotes adhesion following transfection into non-adherent fibroblastic L-cells, reminiscent of a cell adhesion molecule. Currently, no function for Bves in relation to epithelial cell adhesion has been identified. We hypothesize that Bves plays a role at cell junctions to establish and/or modulate cell adhesion or cell-cell interactions in epithelial cell types. In this study, we demonstrate that Bves regulates epithelial integrity and that this function may be associated with a role at the tight junction (TJ). We report that Bves localizes with ZO-1 and occludin, markers of the TJ, in polarized epithelial cell lines and in vivo. We find that the behavior of Bves following low Ca2+ challenge or TPA treatment mimics that observed for ZO-1 and is distinct from adherens junction proteins such as E-cadherin. Furthermore, GST pull-down experiments show an interaction between ZO-1 and the intracellular C-terminal tail of Bves. Finally, we demonstrate that Bves modulates tight junction integrity, as indicated by the loss of transepithelial resistance and junction protein localization at the membrane following Bves knock-down in cultured cells. This study is the first to identify a function for Bves in epithelia and supports the hypothesis that Bves contributes to establishment and/or maintenance of epithelial cell integrity.

Animals↗

PubMed2004

Bves expression during avian embryogenesis.

Bves (blood vessel/epicardial substance) is a transmembrane protein postulated to play a role in cell adhesion. While it is clear that Bves and gene products of the same family are expressed in adult striated muscle cells, the distribution of these proteins during development has not been critically examined. An understanding of the expression pattern of Bves is essential for a determination of protein function and its role in embryogenesis. In this study, we present an expression analysis of Bves during chick gastrulation and germ layer formation. Our data show that Bves is expressed in epithelia of all three germ layers early in development. Furthermore, Bves protein is observed in epithelial tissues during organogenesis, specifically the developing epidermis, the gut endoderm, and the epicardium of the heart. These data support the hypothesis that Bves may play a role in cell adhesion and movement of epithelia during early embryogenesis.

Amino Acid Sequence↗

PubMed2003

Epicardial/Mesothelial cell line retains vasculogenic potential of embryonic epicardium.

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.

Animals↗