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The N-methyl-d-aspartate receptor in heart development: a gene knockdown model using siRNA
Octavian V Lie1, Gregory D Bennett, Thomas H Rosenquist
1Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-5805, United States.
Reproductive Toxicology (Elmsford, N.Y.)
|September 10, 2009
Summary
N-methyl-D-aspartate receptor (NMDAR) antagonists may affect cardiac neural crest (CNC) development. However, blocking the NR1 subunit in avian embryos did not impact heart development, suggesting NMDARs are not essential for CNC function.
Area of Science:
- Developmental biology
- Neuroscience
- Cardiology
Background:
- N-methyl-D-aspartate receptor (NMDAR) antagonists are implicated in conotruncal heart defects.
- The NMDAR's role in cardiac neural crest (CNC) development is not fully understood.
Purpose of the Study:
- To investigate the necessity of the NMDAR NR1 subunit for avian CNC development and heart formation.
- To determine if NMDAR antagonism directly impairs CNC development.
Main Methods:
- Generated a loss-of-function model using small interfering RNA (siRNA) targeting chicken NR1 mRNA in avian embryos.
- Characterized the chicken NR1 gene and protein sequence.
- Analyzed spatiotemporal expression of NR1 in neural tube and pre-migratory CNC sites.
Main Results:
- siRNA effectively reduced NR1 protein expression in pre-migratory CNC.
- Avian embryo survival and cardiac development were not adversely affected by NR1 knockdown.
- NR1 was expressed in the neural tube at sites relevant to CNC migration.
Conclusions:
- The cardiac neural crest can develop normally without functional NMDAR NR1 subunits.
- NMDAR antagonists may impact CNC development through mechanisms beyond direct NR1 subunit impairment.
- Further research is needed to elucidate the complex interactions between NMDARs and CNC development.
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