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Fibronectin signals through integrin α5β1 to regulate cardiovascular development in a cell type-specific manner
Dongying Chen1, Xia Wang2, Dong Liang2
1Sidney Kimmel Medical College of Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA; Cell and Developmental Biology graduate program, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
Developmental Biology
|October 6, 2015
Summary
Fibronectin (Fn1) is crucial for cardiovascular development. Localized Fn1 in pharyngeal arches is essential for forming pharyngeal arch arteries (PAAs) and the cardiac outflow tract.
Area of Science:
- Developmental Biology
- Cardiovascular Biology
- Extracellular Matrix Biology
Background:
- Fibronectin (Fn1) is vital for embryonic development, but its specific role in cardiovascular morphogenesis is unclear due to early lethality in global knockout models.
- Fn1 exhibits non-uniform expression patterns during embryogenesis, with notable enrichment in the pharyngeal region, suggesting a localized function.
Purpose of the Study:
- To investigate the essential role of localized fibronectin (Fn1) in cardiovascular development, particularly in the pharyngeal region.
- To identify the cellular mechanisms and signaling pathways through which Fn1 influences cardiovascular morphogenesis.
Main Methods:
- Conditional ablation of Fn1 using the Isl1(Cre) mouse model to assess its role in cardiovascular development.
- Conditional ablation of integrin α5, a major Fn1 receptor, using the Isl1(Cre) mouse model to investigate Fn1 signaling pathways.
- Detailed analysis of pharyngeal arch artery (PAA) formation, cardiac outflow tract (OFT) development, and ventricular septum integrity in mutant embryos.
Main Results:
- Conditional deletion of Fn1 in Isl1(Cre) mice resulted in defective 4th PAA formation, aberrant OFT development, and ventricular septum defects.
- Deletion of integrin α5 using Isl1(Cre) recapitulated the cardiovascular abnormalities observed in Fn1 conditional mutants.
- Ablation of integrin α5 in specific pharyngeal arch tissues did not cause PAA defects, indicating an extrinsic signaling mechanism.
Conclusions:
- Localized fibronectin in the pharyngeal region is essential for proper cardiovascular development, including PAA and OFT formation.
- Integrin α5-dependent signaling, originating from a source extrinsic to the pharyngeal endothelium, mediates the formation of the 4th PAAs.
- Further research is needed to identify the specific extrinsic signal and its receptor involved in Fn1-mediated cardiovascular morphogenesis.
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