Abstract 14270: The Novel Contribution of Preotic Neural Crest Cells in the Coronary Artery Development
Neural crest cells contribute to many types of tissues. During the heart development, the postotic neural crest, also known as the cardiac neural crest, constitutes the aorticopulmonary septum. Defects of the postotic neural crest cause the persistent truncus arteriosus. However, contribution of the neural crest cells in the ventricular regions in not fully understood. Here we show that the preotic neural crest, which migrates from more anterior region than the postotic neural crest, contributes to the coronary artery smooth muscle cells (CASMCs) and needs for the proper formation of the coronary artery. We also reports that these neural crest-derived CASMCs are influenced by the entothein-1(ET-1)/endothelin A receptor(ETAR) signaling. Fetal coronary angiography revealed some septal branches were abnormally enlarged in both ET-1 and ETAR KO mice at embryonic day 17.5 (E17.5) and the branching pattern of the septal branch was also altered in both KO mice. Immunohistochemical analysis revealed partial lack of CASMCs in KO mice and serial analysis showed these malformations were occurred at the remodeling stage of coronary arteries. Each phenotype appeared in the septal branch-specific manner, then we hypothesized these segment specificities stood on the variety of cell sources of CASMCs. Fate mapping using Wnt1-Cre mice suggested that lacked CASMCs were specifically derived from the neural crest cells. To clarify the contribution of neural crest cells to CASMCs in detail, we used quail-chick chimera technique and neural crest ablation models. Quail-chick chimera with postotic neural crest revealed the massive contribution of quail neural crest cells to the aorticopulmonary septum, however they did not distribute to the coronary vessels. Next we generated the preotic neural crest chimera, in which neural crest cells between midbrain and rhombomere 5 were transplanted. Surprisingly, they preferentially contributed to the CASMCs in the septal branch. Chick ablation models and ETAR antagonist-treated embryos also showed coronary artery malformations similar to those in ET-1 and ETAR KO mice. This is the first report which reveals the contribution of the preotic neural crest, not the postotic neural crest.
- © 2012 by American Heart Association, Inc.