PUBLICATION
4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation
- Authors
- Lee, J., Fei, P., Packard, R.R., Kang, H., Xu, H., Baek, K.I., Jen, N., Chen, J., Yen, H., Kuo, C.J., Chi, N.C., Ho, C.M., Li, R., Hsiai, T.K.
- ID
- ZDB-PUB-160329-6
- Date
- 2016
- Source
- The Journal of Clinical Investigation 126(5): 1679-90 (Journal)
- Registered Authors
- Chi, Neil C.
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Heart Atria/embryology
- Microscopy, Fluorescence/methods
- Myocardial Contraction/physiology*
- Myocardium/cytology
- Myocardium/metabolism*
- Neuregulin-1/genetics
- Neuregulin-1/metabolism
- Organogenesis/physiology*
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Shear Strength*
- Signal Transduction/physiology*
- Troponin T/genetics
- Troponin T/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 27018592 Full text @ Journal of Clin. Invest.
Citation
Lee, J., Fei, P., Packard, R.R., Kang, H., Xu, H., Baek, K.I., Jen, N., Chen, J., Yen, H., Kuo, C.J., Chi, N.C., Ho, C.M., Li, R., Hsiai, T.K. (2016) 4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation. The Journal of Clinical Investigation. 126(5):1679-90.
Abstract
Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis. Reduction of blood viscosity via gata1a morpholino oligonucleotides (MO) reduced shear stress, resulting in downregulation of Notch signaling and attenuation of trabeculation. Arrest of cardiomyocyte contraction either by troponin T type 2a (tnnt2a) MO or in weak atriumm58 (wea) mutants resulted in reduced shear stress and downregulation of Notch signaling and trabeculation. Integrating 4D SPIM imaging with synchronization algorithm demonstrated that coinjection of neuregulin1 mRNA with gata1 MO rescued trabeculation to restore contractile function in association with upregulation of Notch-related genes. Crossbreeding of Tg(flk:mCherry) fish, which allows visualization of the vascular system with the Tg(tp1:gfp) Notch reporter line, revealed that shear stress-mediated Notch activation localizes to the endocardium. Deleting endocardium via the clochesk4 mutants downregulated Notch signaling, resulting in nontrabeculated ventricle. Subjecting endothelial cells to pulsatile flow in the presence of the ADAM10 inhibitor corroborated shear stress-activated Notch signaling to modulate trabeculation.
Errata / Notes
This article is corrected by ZDB-PUB-220906-46.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping