title: Cardiac neural crest ablation results in early endocardial cushion and hemodynamic flow abnormalities.
abstract: Cardiac neural crest cell (CNCC) ablation creates congenital heart defects (CHDs) that resemble those observed in many syndromes with craniofacial and cardiac consequences. The loss of CNCCs causes a variety of great vessel defects, including persistent truncus arteriosus and double-outlet right ventricle. However, because of the lack of quantitative volumetric measurements, less severe defects, such as great vessel size changes and valve defects, have not been assessed. Also poorly understood is the role of abnormal cardiac function in the progression of CNCC-related CHDs. CNCC ablation was previously reported to cause abnormal cardiac function in early cardiogenesis, before the CNCCs arrive in the outflow region of the heart. However, the affected functional parameters and how they correlate with the structural abnormalities were not fully characterized. In this study, using a CNCC-ablated quail model, we contribute quantitative phenotyping of CNCC ablation-related CHDs and investigate abnormal early cardiac function, which potentially contributes to late-stage CHDs. Optical coherence tomography was used to assay early- and late-stage embryos and hearts. In CNCC-ablated embryos at four-chambered heart stages, great vessel diameter and left atrioventricular valve leaflet volumes are reduced. Earlier, at cardiac looping stages, CNCC-ablated embryos exhibit abnormally twisted bodies, abnormal blood flow waveforms, increased retrograde flow percentage, and abnormal cardiac cushions. The phenotypes observed in this CNCC-ablation model were also strikingly similar to those found in an established avian fetal alcohol syndrome model, supporting the contribution of CNCC dysfunction to the development of alcohol-induced CHDs.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; and.
authors.forename: Pei
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; and.
authors.forename: Shi
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Ganga H
authors.initials: GH
authors.lastname: Karunamuni
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; and.|Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Jenkins
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; and rollins@case.edu.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Rollins
mesh_terms: D000818:Animals; D001011:Aorta / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000196:embryology; D004625:Embryo, Nonmammalian; D004694:Endocardial Cushion Defects / Q000000981:diagnostic imaging / Q000196:embryology*; D063647:Fetal Alcohol Spectrum Disorders; D006321:Heart / Q000000981:diagnostic imaging / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000196:embryology; D006351:Heart Valves / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000196:embryology; D053685:Laser Therapy; D009432:Neural Crest / Q000196:embryology / Q000601:surgery*; D009929:Organ Size; D010641:Phenotype; D011651:Pulmonary Artery / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000196:embryology; D011784:Quail; D041623:Tomography, Optical Coherence
keywords: cardiac cushion; cardiac function; cardiac neural crest; cardiac valve; optical coherence tomography