Regulation of Cardiogenesis by GATA Transcription Factors
Abstract
In the first year of this project, we were able to evaluate loss of function mutations for gata4, gata5, and gata6, in bothzebrafish and human ESC models. We were surprised to find that gata4 null mutations were tolerated in zebrafish, while thegata5 and gata6 mutations phenocopied previous analyses including a small truncated heart tube for gata6 mutants. We usedwestern blotting to demonstrate that the gata4 mutation is null. Most strikingly, aged mutant adults showed a severecardiomyopathy. The heart is enlarged at least two-fold in size. We are currently characterizing hearts by histology todetermine if the gata4 mutants may be a model for human dilated cardiomyopathy or some other specific disorder. This is anexciting result that supports our underlying hypothesis that the mutants can be used to model human congenital cardiacdisease. In addition, we found a striking defect in cardiogenesis in the human GATA6 null mutant ESCs. We correlated thiswith a sharp increase in expression of RALDH2, suggesting that GATA6 normally restricts retinoid signaling important forcardiac differentiation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086485
Entities
People
- Todd Evans
Organizations
- Weill Cornell Medicine