FRS2α-dependent cell fate transition during endocardial cushion morphogenesis.

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Cell Biology

Background:

• Atrioventricular valve formation depends on endothelial-to-mesenchymal transition (EndMT).
• Fibroblast growth factor receptor substrate 2-alpha (FRS2α) regulates adult endothelium EndMT via TGFβ signaling.
• The role of endothelial FRS2α in embryonic valve development is unclear.

Purpose of the Study:

• To investigate the function of endothelial FRS2α in embryonic atrioventricular (AV) valve development.
• To determine the impact of FRS2α deletion on EndMT during AV cushion formation and valve maturation.

Main Methods:

• Generation of inducible endothelial-specific FRS2α knockout mice (FRS2α^iECKO).
• Analysis of AV valve development in FRS2α^iECKO embryos with early (E7.5) and late (E10.5) gene deletion.
• Assessment of EndMT and valve morphology.

Main Results:

• Early endothelial deletion of FRS2α (E7.5) resulted in impaired EndMT in AV cushions.
• FRS2α^iECKO embryos exhibited defective AV valve maturation, leading to thickened, abnormal valves.
• Late deletion of FRS2α (E10.5) did not cause AV valve abnormalities.

Conclusions:

• Endothelial FRS2α is crucial for initiating EndMT during early embryonic heart development.
• FRS2α acts as a pivotal regulator of cell fate transitions in EndMT and subsequent valvulogenesis.
• Timing of FRS2α deletion dictates its impact on AV valve formation.