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Published on: January 20, 2013
Temporal-spatial ablation of neural crest in the mouse results in cardiovascular defects
Diego Porras1, Christopher B Brown
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract:
Neural crest cells are thought to play a critical role in human conotruncal morphogenesis and dysmorphogenesis. Much of our understanding of the contribution of neural crest to cardiovascular patterning comes from ablation and transplantation experiments in avian species. Although fate mapping experiments in mice suggests a conservation of function, the functional requirement for neural crest in cardiovascular development in mammals has not been formally tested. We used a novel two component genetic system for the temporal-spatial ablation of neural crest in the mouse. Affected embryos displayed a spectrum of cardiovascular outflow tract defects and aortic arch patterning abnormalities. We show that the severity of the cardiovascular phenotype is directly related to the level and extent of neural crest ablation. This is the first report of cardiac neural crest ablation in mammals, and it provides important insight into the role of the mammalian neural crest during cardiovascular development.
Insights
Neural crest cells are crucial for mammalian cardiovascular development. Ablating these cells in mice caused outflow tract defects, confirming their essential role in heart and vessel formation.
Area of Science:
- Developmental biology
- Cardiovascular science
- Genetics
Background:
- Neural crest cells are implicated in human heart development.
- Avian studies inform our understanding, but mammalian roles remain unconfirmed.
- Previous mouse studies suggested conserved function, but direct testing was lacking.
Purpose of the Study:
- To investigate the functional requirement of neural crest cells in mammalian cardiovascular development.
- To establish a model for temporal-spatial ablation of neural crest cells in mice.
- To characterize the resulting cardiovascular phenotypes.
Main Methods:
- Utilized a novel two-component genetic system for targeted neural crest cell ablation in mouse embryos.
- Analyzed the spectrum of cardiovascular outflow tract defects and aortic arch patterning abnormalities.
- Correlated the severity of defects with the extent of neural crest ablation.
Main Results:
- Demonstrated that neural crest ablation leads to a range of cardiovascular outflow tract defects.
- Observed abnormalities in aortic arch patterning following neural crest cell loss.
- Established a direct relationship between the level of ablation and the severity of cardiovascular phenotypes.
Conclusions:
- This study provides the first direct evidence for the essential role of cardiac neural crest in mammalian cardiovascular development.
- The findings highlight the critical contribution of neural crest cells to normal heart and great vessel formation in mammals.
- Confirms the functional requirement of neural crest in mammalian cardiovascular patterning, extending avian findings.
