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

鸡胚胎发育过程中心脏神经嵴的遗传和分子基础

• 批准号: 6110279
• 负责人: CLAYTON A BUCK
• 金额: --
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-26 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110279
• 关键词: antisense nucleic acid; congenital heart disorder; developmental genetics; embryo /fetus cell /tissue; gene deletion mutation; genetic library; heart transplantation; in situ hybridization; neural crest; nonmammalian vertebrate embryology; northern blottings; nucleic acid sequence; tissue mosaicism

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.

心脏神经脊在支持发育方面是独一无二的。 心脏和主动脉弓动脉。贝弗利·伊曼纽尔博士和 同事们已经证明了人类22q11区域的缺失 22号染色体导致儿童的一系列缺陷，这些缺陷可能是 在去除迁移前心脏神经雏鸡中的模拟 克雷斯特。这些缺陷也存在于16三体小鼠中 包含与人类22q11对应的区域的复制。 我的目标是确定基因产品的功能意义 从22q11开始与神经脊相关的心脏发育。试验性的 将使用产生的嵌合体来建立这种缺失的模型 16-三体小鼠胚胎心脏神经脊移植 变成普通的雏鸟寄主。这些嵌合体胚胎将通过 项目3和项目4用于适当的神经脊移植和 细胞增殖、细胞外基质变异与最终心血管 表型。利用该模型对22q11缺失基因的功能进行了研究 是可以预见的。22q11微缺失的探针将用于 从鸡胚中筛选心脏神经脊富集型c DNA文库。 阳性克隆将被测序，并用于北方和原位 心血管疾病关键期鸡胚发育状况分析 发展。最后，这些编码消息的cDNA 在功能上和时空上与源自 小鼠-小鸡嵌合模型将用于消融或更多 鸡胚胎中的表达研究。