TY  - JOUR
A1  - Paolini, Alessio
A1  - Fontana, Federica
A1  - Van-Cuong Pham, 
A1  - Rödel, Claudia Jasmin
A1  - Seyfried, Salim
T1  - Mechanosensitive Notch-Dll4 and Klf2-Wnt9 signaling pathways intersect in guiding valvulogenesis in zebrafish
JF  - Cell reports
N2  - In the zebrafish embryo, the onset of blood flow generates fluid shear stress on endocardial cells, which are specialized endothelial cells that line the interior of the heart. High levels of fluid shear stress activate both Notch and Klf2 signaling, which play crucial roles in atrioventricular valvulogenesis. However, it remains unclear why only individual endocardial cells ingress into the cardiac jelly and initiate valvulogenesis. Here, we show that lateral inhibition between endocardial cells, mediated by Notch, singles out Delta-like-4-positive endocardial cells. These cells ingress into the cardiac jelly, where they form an abluminal cell population. Delta-like-4-positive cells ingress in response to Wnt9a, which is produced in parallel through an Erk5Klf2-Wnt9a signaling cascade also activated by blood flow. Hence, mechanical stimulation activates parallel mechanosensitive signaling pathways that produce binary effects by driving endocardial cells toward either luminal or abluminal fates. Ultimately, these cell fate decisions sculpt cardiac valve leaflets.
Y1  - 2021
U6  - https://doi.org/10.1016/j.celrep.2021.109782
SN  - 2211-1247
VL  - 37
IS  - 1
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -