PUBLICATION
Effects of Extended Pharmacological Disruption of Zebrafish Embryonic Heart Biomechanical Environment on Cardiac Function, Morphology and Gene Expression
- Authors
- Foo, Y.Y., Motakis, E., Tiang, Z., Shen, S., Lai, J.K.H., Chan, W.X., Wiputra, H., Chen, N., Chen, C.K., Winkler, C., Foo, R.S.Y., Yap, C.H.
- ID
- ZDB-PUB-210601-12
- Date
- 2021
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 250(12): 1759-1777 (Journal)
- Registered Authors
- Lai, Jason, Winkler, Christoph
- Keywords
- BDM stoppage of embryonic heart, Embryonic heart mechanobiology, biofluid dynamics, computational fluid dynamics, embryonic heart biomechanics
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Biomechanical Phenomena/drug effects*
- Biomechanical Phenomena/physiology
- Diacetyl/analogs & derivatives*
- Diacetyl/pharmacology
- Embryo, Nonmammalian/drug effects
- Embryonic Development/drug effects
- Embryonic Development/genetics
- Gene Expression Regulation, Developmental/drug effects
- Heart/drug effects
- Heart/embryology*
- Heart/physiology
- Hydrodynamics
- Myocardial Contraction/drug effects
- Myocardium/metabolism
- Organogenesis/drug effects
- Organogenesis/genetics
- Organogenesis/physiology
- Stress, Mechanical
- Zebrafish*/embryology
- Zebrafish*/genetics
- PubMed
- 34056790 Full text @ Dev. Dyn.
Citation
Foo, Y.Y., Motakis, E., Tiang, Z., Shen, S., Lai, J.K.H., Chan, W.X., Wiputra, H., Chen, N., Chen, C.K., Winkler, C., Foo, R.S.Y., Yap, C.H. (2021) Effects of Extended Pharmacological Disruption of Zebrafish Embryonic Heart Biomechanical Environment on Cardiac Function, Morphology and Gene Expression. Developmental Dynamics : an official publication of the American Association of Anatomists. 250(12):1759-1777.
Abstract
Background Biomechanical stimuli are known to be important to cardiac development, but the mechanisms are not fully understood. Here, we pharmacologically disrupted the biomechanical environment of wildtype zebrafish embryonic hearts for an extended duration and investigated the consequent effects on cardiac function, morphological development, and gene expression.
Results Myocardial contractility was significantly diminished or abolished in zebrafish embryonic hearts treated for 72 hours from 2 dpf with 2,3-butanedione monoxime (BDM). Image-based flow simulations showed that flow wall shear stresses were abolished or significantly reduced with high oscillatory shear indices. At 5 dpf, after removal of BDM, treated embryonic hearts were mal-developed, having disrupted cardiac looping, smaller ventricles, and poor cardiac function (lower ejected flow, bulboventricular regurgitation, lower contractility and slower heart rate). RNA sequencing of cardiomyocytes of treated hearts revealed 922 significantly up-regulated genes and 1698 significantly down-regulated genes. RNA analysis and subsequent qPCR and histology validation suggested that biomechanical disruption led to an upregulation of inflammatory and apoptotic genes, and downregulation of ECM remodelling and ECM-receptor interaction genes. Biomechanics disruption also prevented the formation of ventricular trabeculation along with notch1 and erbb4a downregulation.
Conclusions Extended disruption of biomechanical stimuli caused mal-development, and potential genes responsible for this are identified. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping