Abstract
The formation of cardiac valves depends on mechanical forces exerted by blood flow. Endocardial cells lining the interior of the heart are sensitive to these stimuli and respond by rearranging into luminal cells subjected to shear stress and abluminal cells not exposed to it. The mechanisms by which endocardial cells sense these dynamic biomechanical stimuli and how they evoke different cellular responses are largely unknown. Here, we show that blood flow activates two parallel mechanosensitive pathways, one mediated by Notch and the other by Klf2a. Both pathways negatively regulate the angiogenesis receptor Vegfr3/Flt4, which becomes restricted to abluminal endocardial cells. Its loss disrupts valve morphogenesis and results in the occurrence of Notch signaling within abluminal endocardial cells. Our work explains how antagonistic activities by Vegfr3/Flt4 on the abluminal side and by Notch on the luminal side shape cardiac valve leaflets by triggering unique differences in the fates of endocardial cells.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
