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Analysis of Neural Crest Migration and Differentiation by Cross-species Transplantation
Published on: February 7, 2012
Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis
Dong Liang1, Xia Wang1, Ashok Mittal1
1Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA.
Insights
Integrin α5β1 in mesoderm is crucial for neural crest development and cardiovascular morphogenesis. Ablating it causes severe embryonic defects, including heart and aortic arch abnormalities.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Integrins are essential cell surface receptors mediating cell-matrix and cell-cell interactions.
- Integrin α5β1 plays a role in various developmental processes, but its specific function in early cardiovascular development is not fully understood.
Purpose of the Study:
- To investigate the role of integrin α5β1 in cardiovascular development using a conditional knockout mouse model.
- To determine the impact of ablating integrin α5 in the anterior mesoderm on neural crest and cardiovascular morphogenesis.
Main Methods:
- Utilized Mesp1(Cre) knock-in mice to conditionally ablate integrin α5 in the anterior mesoderm.
- Analyzed embryonic phenotypes, focusing on cardiovascular and neural crest development.
Main Results:
- Mesp1-driven ablation of integrin α5 resulted in mid-gestation embryonic lethality due to severe cardiovascular defects.
- Mutant embryos exhibited neural crest abnormalities, including cleft palate, ventricular septal defects, and defective aortic arch artery remodeling.
- Defects in aortic arch artery remodeling were linked to impaired neural crest cell proliferation and differentiation into vascular smooth muscle cells.
Conclusions:
- Mesodermal integrin α5β1 is essential for proper neural crest development and subsequent cardiovascular morphogenesis.
- Integrin α5β1 mediates critical signaling between mesoderm and neural crest, regulating neural crest-dependent embryonic structure formation.
Abstract:
Integrin α5-null embryos die in mid-gestation from severe defects in cardiovascular morphogenesis, which stem from defective development of the neural crest, heart and vasculature. To investigate the role of integrin α5β1 in cardiovascular development, we used the Mesp1(Cre) knock-in strain of mice to ablate integrin α5 in the anterior mesoderm, which gives rise to all of the cardiac and many of the vascular and muscle lineages in the anterior portion of the embryo. Surprisingly, we found that mutant embryos displayed numerous defects related to the abnormal development of the neural crest such as cleft palate, ventricular septal defect, abnormal development of hypoglossal nerves, and defective remodeling of the aortic arch arteries. We found that defects in arch artery remodeling stem from the role of mesodermal integrin α5β1 in neural crest proliferation and differentiation into vascular smooth muscle cells, while proliferation of pharyngeal mesoderm and differentiation of mesodermal derivatives into vascular smooth muscle cells was not defective. Taken together our studies demonstrate a requisite role for mesodermal integrin α5β1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures.
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