PUBLICATION
Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish
- Authors
- Just, S., Raphel, L., Berger, I.M., Bühler, A., Keßler, M., Rottbauer, W.
- ID
- ZDB-PUB-161203-6
- Date
- 2016
- Source
- PLoS One 11: e0167306 (Journal)
- Registered Authors
- Berger, Ina, Bühler, Anja, Just, Steffen, Keßler, Mirjam, Raphel, Linda, Rottbauer, Wolfgang
- Keywords
- Zebrafish, Embryos, Heart, Hyperexpression techniques, Cardiac ventricles, Transcription factors, DNA sequence analysis, BAC cloning
- MeSH Terms
-
- Animals
- Cell Proliferation
- Ectopic Gene Expression
- Gene Expression Regulation, Developmental*
- Gene Knockdown Techniques
- Heart/embryology*
- Mutation
- Myocytes, Cardiac/metabolism
- Organogenesis/genetics*
- Phenotype
- T-Box Domain Proteins/genetics*
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 27907103 Full text @ PLoS One
Citation
Just, S., Raphel, L., Berger, I.M., Bühler, A., Keßler, M., Rottbauer, W. (2016) Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish. PLoS One. 11:e0167306.
Abstract
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein. Morpholino-mediated knock-down of Tbx20 in wild-type zebrafish embryos phenocopies whz, indicating that the whz phenotype is due to loss of Tbx20 function, thereby leading to significantly reduced cardiomyocyte numbers by impaired proliferation of heart muscle cells. Ectopic overexpression of wild-type Tbx20 in whz mutant embryos restored cardiomyocyte proliferation and heart growth. Interestingly, ectopic overexpression of Tbx20 in wild-type zebrafish embryos resulted, similar to the situation in the embryonic mouse heart, in significantly reduced proliferation rates of ventricular cardiomyocytes, suggesting that Tbx20 activity needs to be tightly fine-tuned to guarantee regular cardiomyocyte proliferation and embryonic heart growth in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping