Neural Crest-Derived Endocardial Cells Required for Heart Valve Development
Abnormalities in cardiac valves, which maintain unidirectional blood flow through the heart, affect 2-3% of people worldwide and are the most common form of structural heart disease (1).Yet the cell types that make up the valve, and how they communicate to direct development and homeostasis, remain poorly understood. Here, we identify a rare, essential population of highly secretory valve…
Cardiac valves, which ensure unidirectional blood flow through the heart, are affected by abnormalities in 2-3% of the global population and represent the most common form of structural heart disease (1). The specific cell types involved in valve development and maintenance, as well as the communication between these cells, have remained poorly understood.
In this study, researchers identified a rare, essential population of highly secretory valve endocardial cells in both mice and humans that originate from migrating neural crest cells. When these cells were deleted in mice, perinatal lethality occurred, accompanied by thickened leaflets, stenosis, and regurgitation, which closely resembled human valve disease.
Moreover, a global disruption of parathyroid hormone-like hormone (PTHlh), a secreted signaling protein uniquely expressed by this subset of endocardial cells, caused valve stenosis and lethality, while neural crest-specific deletion of PTHlh led to similar valve disease, impaired maturation of valvular interstitial cells, and disrupted bone morphogenetic protein signaling.
These findings reveal a previously unrecognized cell type and signaling pathway that is crucial for valve morphogenesis, shedding light on the pathogenesis and potential treatment of human valve defects.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
