BMPER Promotes Epithelial-Mesenchymal Transition in the Developing Cardiac Cushions

Area of Science:

• Cardiovascular Development
• Molecular Biology
• Developmental Biology

Background:

• Cardiac valve formation is crucial for cardiovascular development.
• Bone morphogenetic protein (BMP) signaling regulates valve formation.
• BMPER deficiency leads to mitral valve prolapse, but the mechanism is unclear.

Purpose of the Study:

• To investigate the role of BMPER in cardiac valve development.
• To elucidate the mechanism by which BMPER deficiency causes mitral valve prolapse.
• To determine if BMPER regulates BMP2-mediated signaling during valve formation.

Main Methods:

• Analysis of BMPER knockout (BMPER-/-) embryos.
• In vitro studies using cultured endothelial cells.
• Assessment of epithelial-mesenchymal transition (EMT), cell proliferation, and BMP signaling pathway activation (Smad, Sox9).

Main Results:

• BMPER-/- embryos exhibit dysregulated EMT in cardiac cushions, with increased Sox9-positive cells.
• BMPER directly binds BMP2 and inhibits BMP2-induced Smad activation in endothelial cells.
• BMPER blocks BMP2-induced Sox9 protein increase.
• The canonical BMP pathway is hyperactive in BMPER-/- embryos during EMT.

Conclusions:

• BMPER acts as a negative regulator of BMP2-induced Smad and Sox9 activity during heart valve development.
• BMPER deficiency disrupts cardiac valve formation by dysregulating BMP signaling and EMT.
• BMPER is identified as a key regulator of BMP2-mediated cardiac valve development, offering insights into valvular defects.