
심장 내막의 Notch 신호 경로 활성화는 mTORC2-PKC 경로를 통한 기계적 자극에 의해 조절된다.


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Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) in the atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, the precise mechanism underlying Notch activation remains elusive. By transiently blocking the heartbeat of E9.5 mouse embryos, we found that Notch activation in the arterial endothelium was dependent on its ligand Dll4, whereas the reduced expression of Dll4 in the endocardium led to a ligand-depleted field, allowing Notch to be specifically activated in AVC and OFT by regional increased shear stress. The strong shear stress altered the membrane lipid microdomain structure of endocardial cells, which activated mTORC2 and PKC and promoted Notch1 cleavage even in the absence of strong ligand stimulation. These findings highlight the role of mechanical forces as a primary cue for endocardial patterning and provide insights into the mechanisms underlying congenital heart diseases of endocardial origin.

### Competing Interest Statement

The authors have declared no competing interest.

Mechanical forces pattern endocardial Notch activation via mTORC2-PKC pathway

심장-내막의-notch-활성화에-대한-기계적-힘의-패턴화


심장 내막의 Notch 활성화에 대한 기계적 힘의 패턴화
