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  - 
TY  - JOUR
A1  - Bornhorst, Dorothee
A1  - Seyfried, Salim
T1  - Strong as a hippo’s heart
BT  - Biomechanical hippo signaling during zebrafish cardiac development
JF  - Frontiers in cell and developmental biology
N2  - The heart is comprised of multiple tissues that contribute to its physiological functions. During development, the growth of myocardium and endocardium is coupled and morphogenetic processes within these separate tissue layers are integrated. Here, we discuss the roles of mechanosensitive Hippo signaling in growth and morphogenesis of the zebrafish heart. Hippo signaling is involved in defining numbers of cardiac progenitor cells derived from the secondary heart field, in restricting the growth of the epicardium, and in guiding trabeculation and outflow tract formation. Recent work also shows that myocardial chamber dimensions serve as a blueprint for Hippo signaling-dependent growth of the endocardium. Evidently, Hippo pathway components act at the crossroads of various signaling pathways involved in embryonic zebrafish heart development. Elucidating how biomechanical Hippo signaling guides heart morphogenesis has direct implications for our understanding of cardiac physiology and pathophysiology.
KW  - Hippo signaling
KW  - Yap1/Wwtr1 (Taz)
KW  - cardiac development
KW  - mechanobiology
KW  - endocardium
KW  - myocardium
KW  - zebrafish
KW  - intra-organ-communication
Y1  - 2021
U6  - https://doi.org/10.3389/fcell.2021.731101
SN  - 2296-634X
VL  - 9
SP  - 1
EP  - 10
PB  - Frontiers Media
CY  - Lausanne, Schweiz
ER  - 
TY  - GEN
A1  - Seyfried, Salim
A1  - Rödel, Claudia Jasmin
T1  - Blood flow matters in a zebrafish model of cerebral cavernous malformations
T2  - Circulation research : an official journal of the American Heart Association
Y1  - 2020
U6  - https://doi.org/10.1161/CIRCRESAHA.119.316286
SN  - 0009-7330
SN  - 1524-4571
VL  - 126
IS  - 1
SP  - E1
EP  - E2
PB  - Lippincott Williams & Wilkins
CY  - Baltimore, Md.
ER  -