GENETIC AND MOLECULAR BASIS OF CARDIAC NEURAL CREST IN DEVELOPING CHICK EMBRYO

心脏神经嵴支持发育的能力是独一无二的

The cardiac neural crest is unique in its ability to support development of the heart and aortic arch arteries. Dr. Beverly Emmanuel and colleagues have demonstrated that deletion of the region 22q11 from human chromosome 22 results in a spectrum of defects in children that can be mimicked in the chick of removal of the premigratory cardiac neural crest. These defects are also present in the trisomy 16 mouse which contains duplication of the regions corresponding to 22q11 in humans. My goal is to identify the functional significance of the gene products from 22q11 in neural crest related heart development. An experimental model of this deletion will be established using chimeras produced from transplantation of cardiac neural crest from trisomy 16 mouse embryos onto normal chick hosts. These chimeric embryos will be analyzed by projects 3 and 4 for appropriate neural crest migration and proliferation, extracellular matrix variations and final cardiovascular phenotype. Using this model the function of the deleted genes in 22q11 can be predicted. Probes for the 22q11 microdeletion will be used to screen cardiac neural crest-enriched cDNA libraries from chick embryos. Positive clones will be sequenced and used for Northern and in situ analysis of developing chick embryos at critical stages of cardiovascular development. Finally, those cDNAs that code for messages found to correlate functionally and spatiotemporally with information derived from the mouse-chick chimeric model will be used in ablation or over expression studies in chick embryos.