Requirement for AP-2α in cardiac outflow tract morphogenesis
Requirement for AP-2α in cardiac outflow tract morphogenesis
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DOI：
10.1016/s0925-4773(01)00579-2
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发表时间：
2002-01-01
影响因子：
2.6
通讯作者：
Sucov, HM
中科院分区：
文献类型：
--
作者：
Brewer, S;Jiang, XB;Sucov, HM
大多数表达转录因子基因AP-2 α的发育结构在AP-2 α突变小鼠胚胎中受到损害。由于心脏神经嵴人口是AP-2 α表达的一个突出的网站，因为神经嵴是所需的正常心脏形态发生，我们已经调查了AP-2 α在心脏发育的参与。所有的AP-2 α缺陷胚胎都有发育中心脏流出道的畸形：大多数有右心室双出口，一小部分有持续性动脉干。为了在心脏形态发生期间可视化AP-2 α表达细胞，我们建立了一个新的突变种系等位基因，其中IRES-lacZ序列通过同源重组插入AP-2 α基因座。在E9.5-10.5期间在心脏神经嵴群体中观察到阳性表达（以及先前通过原位杂交研究注意到的AP-2 α表达的其他已知领域），并且当心脏神经嵴迁移到发育心脏的流出道时，大多数在E11.5时消失。重要的是，表达AP-2 α的心脏神经嵴的分布在正常和突变胚胎中似乎是相同的。从这个分析中，我们提出，AP-2alpha基因的功能在神经嵴谱系，AP-2alpha是不需要神经嵴细胞迁移，并正常AP-2alpha基因功能需要E11.5之前。AP-2 α可能参与神经嵴和下咽区域周围组织之间的相互作用，从而促进正常的流出道形态发生。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Most developing structures that express the transcription factor gene AP-2alpha are compromised in AP-2alpha mutant mouse embryos. Since the cardiac neural crest population is one prominent site of AP-2alpha expression, and because the neural crest is known to be required for normal cardiac morphogenesis, we have investigated the involvement of AP-2alpha in cardiac development. All AP-2alpha-deficient embryos examined had malformations of the outflow tract of the developing heart: most had double outlet right ventricle, and a small fraction had persistent truncus arteriosus. To visualize AP-2alpha-expressing cells during the period of cardiac morphogenesis, we established a new mutant germline allele in which an IRES-lacZ sequence was inserted by homologous recombination into the AP-2alpha locus. Positive expression was observed in the cardiac neural crest population during the E9.5-10.5 period (as well as in other known domains of AP-2alpha expression previously noted by in situ hybridization studies), and was mostly extinguished by E11.5 when the cardiac neural crest has migrated into the outflow tract of the developing heart. Importantly, the distribution of AP-2alpha-expressing cardiac neural crest appeared to be identical in normal and mutant embryos. From this analysis, we propose that the AP-2alpha gene functions within the neural crest lineage, that AP-2alpha is not required for neural crest cell migration, and that normal AP-2alpha gene function is required prior to E11.5. AP-2alpha may be involved in an interaction between neural crest and surrounding tissues in the subpharyngeal region, thereby promoting normal outflow tract morphogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.