An essential role for connexin43 gap junctions in mouse coronary artery development

Area of Science:

• Cardiovascular Development
• Cellular Biology
• Developmental Biology

Background:

• Connexin43 (Cx43) is essential for neonatal survival, with its absence causing conotruncal heart malformations.
• Neural crest cells have been implicated in cardiac anomalies, but other cell types may also play a role.

Purpose of the Study:

• To investigate the role of proepicardial cells in cardiac development and connexin43 function.
• To determine if connexin43 in proepicardial cells contributes to coronary artery patterning defects.

Main Methods:

• Analysis of connexin43 knockout mouse hearts for cellular abnormalities and coronary artery defects.
• Functional assessment of proepicardial cell coupling, proliferation, and migration.
• Comparison with transgenic mice with neural crest-specific connexin43 inhibition.

Main Results:

• Connexin43 knockout hearts show abnormal fibroblast and vascular smooth muscle cells in infundibular pouches.
• Cx43 knockout mice exhibit diverse coronary artery patterning defects.
• Proepicardial cells express connexin43, and its loss reduces cell coupling, increasing proliferation and migration speeds.
• Neural crest-specific Cx43 inhibition did not replicate these proepicardial cell changes.

Conclusions:

• Connexin43 plays a significant role in coronary artery patterning, involving both proepicardial and cardiac neural crest cells.
• Dysfunctional connexin43 in proepicardial cells contributes to cardiac malformations.
• Connexin43's role in cardiovascular anomalies warrants further investigation in human diseases.