Search

The avian embryo has long been a popular model system in developmental biology. The easy accessibility of the embryo makes it particularly suitable for in ovo microsurgery and manipulation. Re-incubation of the embryo allows long-term follow-up of these procedures. The current review focuses on the variety of techniques available to study development of the cardiac conduction system in avian embryos. Based on the large amount of relevant data arising from experiments in avian embryos, we conclude that the avian embryo has and will continue to be a powerful model system to study development in general and the developing cardiac conduction system in particular., (Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Background: Sinus node dysfunction is frequently observed in patients with congenital heart disease (CHD). Variants in the Vascular Endothelial Growth Factor-A (VEGF) pathway are associated with CHD. In Vegf(120/120) mice, over-expressing VEGF120, a reduced sinoatrial node (SAN) volume was suggested. Aim of the study is to assess the effect of VEGF over-expression on SAN development and function., Methods: Heart rate was measured in Vegf(120/120) and wildtype (WT) embryos during high frequency ultrasound studies at embryonic day (E)12.5, 14.5 and 17.5 and by optical mapping at E12.5. Morphology was studied with several antibodies. SAN volume estimations were performed, and qualitative-PCR was used to quantify expression of genes in SAN tissues of WT and Vegf(120/120) embryos., Results: Heart rate was reduced in Vegf(120/120) compared with WT embryos during embryonic echocardiography (52 ± 17 versus 125 ± 31 beats per minute (bpm) at E12.5, p<0.001; 123 ± 37 vs 160 ± 29 bmp at E14.5, p=0.024; and 177 ± 30 vs 217 ± 34 bmp, at E17.5 p=0.017) and optical mapping (81 ± 5 vs 116 ± 8 bpm at E12.5; p=0.003). The SAN of mutant embryos was smaller and more vascularized, and showed increased expression of the fast conducting gap junction protein, Connexin43., Conclusions: Over-expression of VEGF120 results in reduced heart rate and a smaller, less compact and hypervascularized SAN with increased expression of Connexin43. This indicates that VEGF is necessary for normal SAN development and function., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The cardiac conduction system is a specialized network that initiates and closely coordinates the heart beat. Cardiac conduction system development is intricately related to the development and maturation of the embryonic heart towards its four-chambered form, as is indicated by the fact that disturbed development of cardiac structures is often accompanied by a disturbed formation of the CCS. Electrophysiological studies have shown that selected conduction disturbances and cardiac arrhythmias do not take place randomly in the heart but rather at anatomical predilection sites. Knowledge on development of the CCS may facilitate understanding of the etiology of arrhythmogenic events. In this review we will focus on embryonic development of the CCS in relation to clinical arrhythmias, as well as on specific cardiac conduction abnormalities that are observed in patients with congenital heart disease., (Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Background: Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) in the mouse is expressed in the developing cardiac conduction system (CCS). In the sinoatrial node (SAN), HCN4 is the predominant isoform responsible for the funny current. To date, no data are available on HCN4 expression during chicken CCS development., Objective: The purpose of this study was to provide the full-length sequence of Hcn4 and describe its expression pattern during development in relation to the CCS in the chicken embryo., Methods: Hcn4 RNA expression was studied by in situ hybridization in sequential chick developmental stages (HH11-HH35) and immunohistochemical staining was conducted for the myocardial protein cardiac troponin I and the cardiac transcription factor Nkx2.5., Results: We obtained the full-length sequence of Hcn4 in chick. Hcn4 expression was observed early in development in the primary heart tube. At later stages, expression became restricted to transitional zones flanked by working myocardium, comprising the sinus venosus myocardium where the SAN develops, the atrioventricular canal myocardium, the primary fold (a myocardial zone between the developing ventricles), and the developing outflow tract. Further in development, Hcn4 expression was restricted to the SAN, the atrioventricular node, the common bundle, the bundle branches, and the internodal and atrioventricular ring myocardium., Conclusion: We have identified Hcn4 as a marker of the developing CCS in the chick. The primary heart tube expresses Hcn4, which is later restricted to the transitional zones and eventually the elements of the mature CCS. Furthermore, we hypothesize that expression patterns during development may delineate potential arrhythmogenic sites in the adult heart., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)