PUBLICATION
MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis
- Authors
- Muncie-Vasic, J.M., Sinha, T., Clark, A.P., Brower, E.F., Saucerman, J.J., Black, B.L., Bruneau, B.G.
- ID
- ZDB-PUB-250830-10
- Date
- 2025
- Source
- Genes & Development : (Journal)
- Registered Authors
- Black, Brian
- Keywords
- cardiogenesis, developmental biology, embryogenesis, gene regulation, gene regulatory networks, heart development
- MeSH Terms
-
- Animals
- Enhancer Elements, Genetic
- Gene Expression Regulation, Developmental*
- Gene Regulatory Networks*/genetics
- Heart*/embryology
- MEF2 Transcription Factors*/genetics
- MEF2 Transcription Factors*/metabolism
- Morphogenesis*/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40883017 Full text @ Genes & Dev.
Citation
Muncie-Vasic, J.M., Sinha, T., Clark, A.P., Brower, E.F., Saucerman, J.J., Black, B.L., Bruneau, B.G. (2025) MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis. Genes & Development. :.
Abstract
The gene regulatory networks (GRNs) that control early heart formation are beginning to be understood, but lineage-specific GRNs remain largely undefined. We investigated networks controlled by the vital transcription factor MEF2C using a time course of single-nucleus RNA sequencing and ATAC sequencing in wild-type and Mef2c-null embryos. We identified a "posteriorized" cardiac gene signature and chromatin landscape in the absence of MEF2C. Integrating our multiomics data in a deep learning-based model, we constructed developmental trajectories for each of the outflow tract, ventricular, and inflow tract segments and alterations of these in Mef2c-null embryos. We computationally identified segment-specific MEF2C-dependent enhancers with activity in the developing zebrafish heart. Finally, using inferred GRNs, we discovered that the Mef2c-null heart malformations are partly driven by increased activity of the nuclear hormone receptor NR2F2. Our results delineate lineage-specific GRNs in the early heart tube and provide a generalizable framework for dissecting transcriptional networks governing developmental processes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping