Wnt11 regulates cardiac chamber development and disease during perinatal maturation

摘要: Ventricular chamber growth and development during perinatal circulatory transition is critical for functional adaptation of the heart. However, chamber-specific programs neonatal heart are poorly understood. We used integrated systems genomic biology analyses specific transcriptome we identified Wnt11 as a prominent regulator proliferation. Importantly, downregulation expression was associated with cyanotic congenital defect (CHD) phenotypes correlated O2 saturation levels in hypoxemic infants Tetralogy Fallot (TOF). Perinatal hypoxia treatment mice suppressed induced myocyte proliferation more robustly right ventricle, modulating Rb1 protein activity. inactivation sufficient to induce mouse hearts reduced phosphorylation cardiomyocytes. Finally, downregulated TOF infantile suppression induction markers. This study revealed previously uncharacterized function Wnt11-mediated signaling an important player programming influences pathogenesis response CHDs. Defining underlying regulatory mechanism may yield therapies born