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Erg is a crucial regulator of endocardial-mesenchymal transformation during cardiac valve morphogenesis.

Vijayaraj P, Le Bras A, Mitchell N, Kondo M, Juliao S, Wasserman M, Beeler D, Spokes K, Aird WC, Baldwin HS, Oettgen P - Development (2012)

Bottom Line: Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes.The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells.We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

ABSTRACT
During murine embryogenesis, the Ets factor Erg is highly expressed in endothelial cells of the developing vasculature and in articular chondrocytes of developing bone. We identified seven isoforms for the mouse Erg gene. Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes. The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells. Homozygous Erg(ΔEx3/ΔEx3) knockout mice are viable, fertile and do not display any overt phenotype. By contrast, homozygous Erg(ΔEx4/ΔEx4) knockout mice are embryonic lethal, which is associated with a marked reduction in endocardial-mesenchymal transformation (EnMT) during cardiac valve morphogenesis. We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

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Related in: MedlinePlus

Endocardial cells maintain their adherens junctions in ErgΔEx4/ΔEx4 embryos. (A,B) Heart sections from E10.5 Erg+/+ and ErgΔEx4/ΔEx4 mouse embryos stained for VE-cadherin reveal that the endocardial cells maintain their adherens junctions and fail to invade the cardiac jelly in the mutants. Arrowheads, VE-cadherin staining. (C-F) Lung bud sections of E10.5 Erg+/+ and ErgΔEx4/ΔEx4 embryos reveal a reduction in VE-cadherin staining in the mutant. A, atrium; AVC, atrioventricular canal.
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Figure 10: Endocardial cells maintain their adherens junctions in ErgΔEx4/ΔEx4 embryos. (A,B) Heart sections from E10.5 Erg+/+ and ErgΔEx4/ΔEx4 mouse embryos stained for VE-cadherin reveal that the endocardial cells maintain their adherens junctions and fail to invade the cardiac jelly in the mutants. Arrowheads, VE-cadherin staining. (C-F) Lung bud sections of E10.5 Erg+/+ and ErgΔEx4/ΔEx4 embryos reveal a reduction in VE-cadherin staining in the mutant. A, atrium; AVC, atrioventricular canal.

Mentions: At E10.5, many ErgΔEx4/ΔEx4 embryos exhibited pericardial effusions (Fig. 7K,L), a classic sign of cardiac dysfunction. β-galactosidase-stained sections of control and ErgΔEx4/ΔEx4 embryos that had reached similar developmental stage revealed trabeculae that were well connected to the myocardium of the ventricular wall, and the β-galactosidase-stained ECs lined the trabeculae in both the Erg+/+ and ErgΔEx4/ΔEx4 heart (Fig. 9A,B). We observed regional swellings of the extracellular matrix in the AVC and OFT (Fig. 9C-F) of the heart in both control and mutant embryos; however, invasion of the mesenchyme was dramatically decreased in the mutants (Fig. 9D,F). The endocardial cells maintained their adherens junctions and failed to invade the cardiac extracellular matrix, as observed by VE-cad staining of the AVC and OFT (Fig. 10A,B). By contrast, VE-cad in other tissues, such as the developing lung (Fig. 10C-F), showed a significant reduction in the knockouts compared with wild-type controls.


Erg is a crucial regulator of endocardial-mesenchymal transformation during cardiac valve morphogenesis.

Vijayaraj P, Le Bras A, Mitchell N, Kondo M, Juliao S, Wasserman M, Beeler D, Spokes K, Aird WC, Baldwin HS, Oettgen P - Development (2012)

Endocardial cells maintain their adherens junctions in ErgΔEx4/ΔEx4 embryos. (A,B) Heart sections from E10.5 Erg+/+ and ErgΔEx4/ΔEx4 mouse embryos stained for VE-cadherin reveal that the endocardial cells maintain their adherens junctions and fail to invade the cardiac jelly in the mutants. Arrowheads, VE-cadherin staining. (C-F) Lung bud sections of E10.5 Erg+/+ and ErgΔEx4/ΔEx4 embryos reveal a reduction in VE-cadherin staining in the mutant. A, atrium; AVC, atrioventricular canal.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3472597&req=5

Figure 10: Endocardial cells maintain their adherens junctions in ErgΔEx4/ΔEx4 embryos. (A,B) Heart sections from E10.5 Erg+/+ and ErgΔEx4/ΔEx4 mouse embryos stained for VE-cadherin reveal that the endocardial cells maintain their adherens junctions and fail to invade the cardiac jelly in the mutants. Arrowheads, VE-cadherin staining. (C-F) Lung bud sections of E10.5 Erg+/+ and ErgΔEx4/ΔEx4 embryos reveal a reduction in VE-cadherin staining in the mutant. A, atrium; AVC, atrioventricular canal.
Mentions: At E10.5, many ErgΔEx4/ΔEx4 embryos exhibited pericardial effusions (Fig. 7K,L), a classic sign of cardiac dysfunction. β-galactosidase-stained sections of control and ErgΔEx4/ΔEx4 embryos that had reached similar developmental stage revealed trabeculae that were well connected to the myocardium of the ventricular wall, and the β-galactosidase-stained ECs lined the trabeculae in both the Erg+/+ and ErgΔEx4/ΔEx4 heart (Fig. 9A,B). We observed regional swellings of the extracellular matrix in the AVC and OFT (Fig. 9C-F) of the heart in both control and mutant embryos; however, invasion of the mesenchyme was dramatically decreased in the mutants (Fig. 9D,F). The endocardial cells maintained their adherens junctions and failed to invade the cardiac extracellular matrix, as observed by VE-cad staining of the AVC and OFT (Fig. 10A,B). By contrast, VE-cad in other tissues, such as the developing lung (Fig. 10C-F), showed a significant reduction in the knockouts compared with wild-type controls.

Bottom Line: Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes.The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells.We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

ABSTRACT
During murine embryogenesis, the Ets factor Erg is highly expressed in endothelial cells of the developing vasculature and in articular chondrocytes of developing bone. We identified seven isoforms for the mouse Erg gene. Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes. The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells. Homozygous Erg(ΔEx3/ΔEx3) knockout mice are viable, fertile and do not display any overt phenotype. By contrast, homozygous Erg(ΔEx4/ΔEx4) knockout mice are embryonic lethal, which is associated with a marked reduction in endocardial-mesenchymal transformation (EnMT) during cardiac valve morphogenesis. We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.

Show MeSH
Related in: MedlinePlus