Expression of active Notch1 in avian coronary development.
Notch1 is an important regulator of intercellular interactions in cardiovascular development. We show that the nuclear-localized, cleaved and active form of Notch1, the Notch1 intracellular domain (N1ICD), appeared in mesothelial cells of the pro-epicardium during epicardial formation at looped heart stages. N1ICD was also present in mesothelial cells and mesenchymal cells specifically within the epicardium at sulcus regions. N1ICD-positive endothelial cells were detected within the nascent vessel plexus at the atrioventricular junction and within the compact myocardium (Hamburger and Hamilton stage [HH] 25-HH30). The endothelial cells expressing N1ICD were surrounded by N1ICD-positive smooth muscle cells after coronary orifice formation (HH32-HH35), while N1ICD expression was absent in the mesenchymal and mesothelial cells surrounding mature coronary vessels. We propose that differential activation of the hypoxia/HIF1-VEGF-Notch pathway may play a role in epicardial cell interactions that promote epicardial epithelial/mesenchymal transition and coronary progenitor cell differentiation during epicardial development and coronary vasculogenesis in particularly hypoxic sulcus regions.
Yang
Ke
K
Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Doughman
Yong-Qiu
YQ
Karunamuni
Ganga
G
Gu
Shi
S
Yang
Yu-Chung
YC
Bader
David M
DM
Watanabe
Michiko
M
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D003331:Coronary Vessels / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D011784:Quail; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*
D051881:Receptor, Notch1