Connexin 43 regulates epicardial cell polarity and migration in coronary vascular development

• DOI: 10.1242/dev.032334
• Publication Date: 2009-08-21T18:01:40Z
• Authors: David Y. Rhee; Xiao-Qing Zhao; Richard J. B. Fra...; Guo Ying Huang; John D. Mably; Cecilia W. Lo
• Keywords: Cell polarity; Podocalyxin

Connexin 43 knockout (Cx43 KO) mice exhibit conotruncal malformations and coronary artery defects. We observed epicardial blisters in the Cx43 KO hearts that suggest defects epithelial-mesenchymal transformation(EMT), a process generates vascular progenitors. Analysis using three-dimensional collagen gel invasion assay showed cells are less invasive that, unlike wild-type cells, they fail to organize into thin vessel-like projections. Examination of Wt1 as an marker revealed disorganized pattern cell infiltration. Time-lapse imaging motion analysis explants defect directional migration. This was associated with changes actin/tubulin cytoskeleton. A polarity indicated by failure microtubule-organizing center align direction Forced expression constructs tubulin-binding domain is required for modulation motility. Pecam staining early remodeling primitive plexuses heart. Together, these findings development arising from global perturbation cytoarchitecture cell. Consistent this, we found aberrant myocardialization outflow tract, also known be EMT dependent. cardiac arise disruption polarity, may dependent on Cx43-tubulin interactions.