PUBLICATION
PDGFRA is a conserved HAND2 effector during early cardiac development
- Authors
- Xu, Y., Gehlot, R., Capon, S.J., Albu, M., Gretz, J., Bloomekatz, J., Mattonet, K., Vucicevic, D., Talyan, S., Kikhi, K., Günther, S., Looso, M., Firulli, B.A., Sanda, M., Firulli, A.B., Lacadie, S.A., Yelon, D., Stainier, D.Y.R.
- ID
- ZDB-PUB-241211-5
- Date
- 2024
- Source
- Nature cardiovascular research 3(12): 1531-1548 (Journal)
- Registered Authors
- Albu, Marga, Bloomekatz, Joshua, Capon, Sam, Stainier, Didier, Yelon, Deborah
- Keywords
- none
- Datasets
- GEO:GSE241049, GEO:GSE241971
- MeSH Terms
-
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Myocytes, Cardiac*/metabolism
- Heart/embryology
- Animals, Genetically Modified
- Cell Movement/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Signal Transduction/genetics
- Mice
- Mouse Embryonic Stem Cells/cytology
- Mouse Embryonic Stem Cells/metabolism
- Binding Sites
- Animals
- Organogenesis/genetics
- Basic Helix-Loop-Helix Transcription Factors*/genetics
- Basic Helix-Loop-Helix Transcription Factors*/metabolism
- Mutation
- Gene Expression Regulation, Developmental*
- Phenotype
- Receptor, Platelet-Derived Growth Factor alpha*/genetics
- Receptor, Platelet-Derived Growth Factor alpha*/metabolism
- PubMed
- 39658721 Full text @ Nat Cardiovasc Res
Citation
Xu, Y., Gehlot, R., Capon, S.J., Albu, M., Gretz, J., Bloomekatz, J., Mattonet, K., Vucicevic, D., Talyan, S., Kikhi, K., Günther, S., Looso, M., Firulli, B.A., Sanda, M., Firulli, A.B., Lacadie, S.A., Yelon, D., Stainier, D.Y.R. (2024) PDGFRA is a conserved HAND2 effector during early cardiac development. Nature cardiovascular research. 3(12):1531-1548.
Abstract
The basic helix-loop-helix transcription factor HAND2 has multiple roles during vertebrate organogenesis, including cardiogenesis. However, much remains to be uncovered about its mechanism of action. Here, we show the generation of several hand2 mutant alleles in zebrafish and demonstrate that dimerization-deficient mutants display the null phenotype but DNA-binding-deficient mutants do not. Rescue experiments with Hand2 variants using a newly identified hand2 enhancer confirmed these observations. To identify Hand2 effectors critical for cardiogenesis, we analyzed the transcriptomes of hand2 loss- and gain-of-function embryonic cardiomyocytes and tested the function of eight candidate genes in vivo; pdgfra was most effective in rescuing myocardial migration in hand2 mutants. Accordingly, we identified a putative Hand2-binding region in the zebrafish pdgfra locus that is important for its expression. In addition, Hand2 loss- and gain-of-function experiments in mouse embryonic stem cell-derived cardiac cells decreased and increased Pdgfra expression, respectively. Altogether, these results further our mechanistic understanding of HAND2 function during early cardiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping