PUBLICATION
Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function
- Authors
- Garavito-Aguilar, Z.V., Riley, H.E., and Yelon, D.
- ID
- ZDB-PUB-100826-3
- Date
- 2010
- Source
- Development (Cambridge, England) 137(19): 3215-3220 (Journal)
- Registered Authors
- Yelon, Deborah
- Keywords
- Zebrafish, Heart morphogenesis, Lateral plate mesoderm, Hand2, Fibronectin
- Datasets
- GEO:GSE23381
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Basic Helix-Loop-Helix Transcription Factors/deficiency
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism*
- Cell Polarity
- Epithelial Cells/cytology
- Epithelial Cells/metabolism
- Fibronectins/genetics
- Fibronectins/metabolism*
- Gene Expression Regulation, Developmental
- Heart/embryology*
- Mutation
- Myocardium/cytology
- Myocardium/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 20724450 Full text @ Development
Citation
Garavito-Aguilar, Z.V., Riley, H.E., and Yelon, D. (2010) Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function. Development (Cambridge, England). 137(19):3215-3220.
Abstract
Heart formation requires the fusion of bilateral cardiomyocyte populations as they move towards the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide in zebrafish the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that it plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping