PUBLICATION
FGF signaling enforces cardiac chamber identity in the developing ventricle
- Authors
- Pradhan, A., Zeng, X.I., Sidhwani, P., Marques, S.R., George, V., Targoff, K.L., Chi, N.C., Yelon, D.
- ID
- ZDB-PUB-170227-11
- Date
- 2017
- Source
- Development (Cambridge, England) 144(7): 1328-1338 (Journal)
- Registered Authors
- Chi, Neil C., George, Vanessa, Pradhan, Arjana, Targoff, Kimara, Yelon, Deborah, Zeng, Sean
- Keywords
- amhc, atrium, nkx2.5, ventricle, vmhc, zebrafish
- MeSH Terms
-
- Animals
- Cell Differentiation
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Fibroblast Growth Factors/metabolism*
- Gene Expression Regulation, Developmental
- Heart Atria/cytology
- Heart Ventricles/cytology
- Heart Ventricles/embryology*
- Heart Ventricles/metabolism*
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Organogenesis*/genetics
- Signal Transduction*/genetics
- Time Factors
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism
- PubMed
- 28232600 Full text @ Development
Citation
Pradhan, A., Zeng, X.I., Sidhwani, P., Marques, S.R., George, V., Targoff, K.L., Chi, N.C., Yelon, D. (2017) FGF signaling enforces cardiac chamber identity in the developing ventricle. Development (Cambridge, England). 144(7):1328-1338.
Abstract
Atrial and ventricular cardiac chambers behave as distinct subunits with unique morphological, electrophysiological, and contractile properties. Despite the importance of chamber-specific features, chamber fate assignments remain relatively plastic, even after differentiation is underway. In zebrafish, Nkx transcription factors are essential for the maintenance of ventricular characteristics, but the signaling pathways that operate upstream of Nkx factors in this context are not well understood. Here, we show that FGF signaling plays an essential part in enforcing ventricular identity. Loss of FGF signaling results in a gradual accumulation of atrial cells, a corresponding loss of ventricular cells, and the appearance of ectopic atrial gene expression within the ventricle. These phenotypes reflect important roles for FGF signaling in promoting ventricular traits, both in early-differentiating cells that form the initial ventricle and in late-differentiating cells that append to its arterial pole. Moreover, we find that FGF signaling functions upstream of nkx genes to inhibit ectopic atrial gene expression. Together, our data suggest a model in which sustained FGF signaling acts to suppress cardiomyocyte plasticity and to preserve the integrity of the ventricular chamber.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping