Mechanosensitive Notch-Dll4 and Klf2-Wnt9 signaling pathways intersect in guiding valvulogenesis in zebrafish
- 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 decisionsIn 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.…
Author details: | Alessio PaoliniORCiDGND, Federica FontanaGND, Van-Cuong Pham, Claudia Jasmin RödelORCiD, Salim SeyfriedORCiDGND |
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DOI: | https://doi.org/10.1016/j.celrep.2021.109782 |
ISSN: | 2211-1247 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/34610316 |
Title of parent work (English): | Cell reports |
Publisher: | Cell Press |
Place of publishing: | Maryland Heights, MO |
Publication type: | Article |
Language: | English |
Date of first publication: | 2021/10/05 |
Publication year: | 2021 |
Release date: | 2023/07/14 |
Volume: | 37 |
Issue: | 1 |
Article number: | 109782 |
Number of pages: | 13 |
Funding institution: | Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [SE2016/7-2, SE2016/10-1, SE2016/13-1]; DFGGerman Research Foundation (DFG)European Commission [SFB958, INST 336/114-1 FUGG, INST 336/104-1]; Marie Curie ITN V.A.Cure; DZHK |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Peer review: | Referiert |
Publishing method: | Open Access / Gold Open-Access |
DOAJ gelistet | |
License (German): | CC-BY-NC-ND - Namensnennung, nicht kommerziell, keine Bearbeitungen 4.0 International |