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Role of PAX3 in the conotruncal septation of the developing heart

PAX3 在发育中心脏圆锥干分隔中的作用

基本信息

批准号：
12670746
负责人：
FUJINO Hidetoshi
金额：
$ 1.73万
依托单位：
Shiga University Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670746/
关键词：
PAX3 Sox4 bis-diamine cardiac development conotruncal septation neural tube closure neural crest cell RT-RCP

项目摘要

1. A single dose of bis-diamine was administered to pregnant ICR mice on 7.5 days of gestation and the expression of PAX3 m-RNA in the embryonic nervous system was examined using semi-quantitative RT-PCR method. The control embryos showed PAX3 expression in the central nervous system was first detected on 8.5 embryonic day (ED), reached the maximum level on 11.5 and diminished on 13.5 ED. The treated embryos demonstrated the same expressional pattern of the control embryos and no significant difference in the amount of m-RNA was seen between the control and treated embryos.2. Expressions of transcriptional factors important for the development of the central nervous system were evaluated in the mice embryos treated with bis-diamine. Expression of EMX-1 was significantly reduced on 10.5 and 1 1.5 ED in the embryonic brain treated with bis-diamine, compared with that in control embryos. Expressional patterns of Wnt-3 and AP-2 were not affected by bis-diamine administration.3. Sox4 is a Sry-box family of transcriptional factors and exclusively expressed in the conal ridge of the outflow tract and the atrioventricular canal of embryonic hearts. The gene disruption in mice causes abnormal development of the semilunar valves, resulting in cardiac anomalies such as infundibular ventricular septal defect and persistent truncus arteriosus. Sox4 expressions in the embryonic brain and heart were down-regulated by bis-diamine administration.Expressional pattern of m-RNA shown in this study indicated that bis-diamine affected the development of the central nervous system and, subsequently, disturbed migration of neural crest cells into the heart. The contribution of PAX3 to the conotruncal septaion was not clear in this study. Sox4 may be involved in the migration of neural crest cells and the differentiation to the vascular smooth muscle cells.

1.在孕7.5d时，给ICR小鼠单次注射双二胺，用半定量RT-PCR方法检测胚胎神经系统PAX 3 mRNA的表达。对照组胚胎在胚胎发育的第8.5天（艾德）开始检测到PAX 3在中枢神经系统的表达，在胚胎发育的第11.5天达到最高水平，在胚胎发育的第13.5天开始下降.在用双二胺处理的小鼠胚胎中评价对中枢神经系统发育重要的转录因子的表达。与对照胚胎相比，在10.5和11.5艾德ED时，双二胺处理的胚胎脑中EMX-1的表达显著降低。Wnt-3和AP-2的表达模式不受双二胺的影响. Sox 4是一个Sry-box转录因子家族，仅在胚胎心脏流出道的圆锥嵴和房室管中表达。小鼠的基因破坏导致半月瓣发育异常，导致心脏畸形，如漏斗部室间隔缺损和持续性动脉干。双二胺可下调胚胎脑和心脏中Sox 4的表达，其mRNA的表达模式表明双二胺影响中枢神经系统的发育，进而影响神经嵴细胞向心脏的迁移。PAX 3在锥体干分隔中的作用尚不清楚。Sox 4可能参与神经嵴细胞的迁移和向血管平滑肌细胞的分化。