PUBLICATION
Mechanosensitive Notch-Dll4 and Klf2-Wnt9 signaling pathways intersect in guiding valvulogenesis in zebrafish
- Authors
- Paolini, A., Fontana, F., Pham, V.C., Rödel, C.J., Abdelilah-Seyfried, S.
- ID
- ZDB-PUB-211006-10
- Date
- 2021
- Source
- Cell Reports 37: 109782 (Journal)
- Registered Authors
- Keywords
- Delta-like 4, Klf2, Notch1, Wnt9, endocardium, mechanotransduction, valvulogenesis, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/metabolism
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/pathology
- Embryonic Development
- Endocardium/cytology
- Endocardium/metabolism*
- Heart Valves/growth & development
- Heart Valves/metabolism
- Heart Valves/pathology
- Intracellular Signaling Peptides and Proteins/antagonists & inhibitors
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/metabolism
- Mechanotransduction, Cellular*
- Mitogen-Activated Protein Kinase 7/metabolism
- Morpholinos/metabolism
- Receptors, Neurotransmitter/antagonists & inhibitors
- Receptors, Neurotransmitter/genetics
- Receptors, Neurotransmitter/metabolism
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Signal Transduction*
- Wnt Proteins/antagonists & inhibitors
- Wnt Proteins/genetics
- Wnt Proteins/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34610316 Full text @ Cell Rep.
Citation
Paolini, A., Fontana, F., Pham, V.C., Rödel, C.J., Abdelilah-Seyfried, S. (2021) Mechanosensitive Notch-Dll4 and Klf2-Wnt9 signaling pathways intersect in guiding valvulogenesis in zebrafish. Cell Reports. 37:109782.
Abstract
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 Erk5-Klf2-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping