Brewer Stephanie, Jiang Xiaobing, Donaldson Stephanie, Williams Trevor, Sucov Henry M
Department of Molecular, Cellular, and Developmental Biology, Yale University, 266 Whitney Avenue, KBT 1034, New Haven, CT 06511, USA.
Mech Dev. 2002 Jan;110(1-2):139-49. doi: 10.1016/s0925-4773(01)00579-2.
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.
大多数表达转录因子基因AP - 2α的正在发育的结构在AP - 2α突变小鼠胚胎中都受到了损害。由于心脏神经嵴群体是AP - 2α表达的一个主要部位，并且已知神经嵴是正常心脏形态发生所必需的，我们研究了AP - 2α在心脏发育中的作用。所有检查的AP - 2α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，一小部分有永存动脉干。为了在心脏形态发生期间可视化表达AP - 2α的细胞，我们建立了一个新的突变种系等位基因，其中通过同源重组将一个IRES - lacZ序列插入到AP - 2α基因座中。在E9.5 - 10.5期间在心脏神经嵴群体中观察到阳性表达（以及在先前原位杂交研究中指出的AP - 2α表达的其他已知区域），并且当心脏神经嵴迁移到发育中心脏的流出道时，在E11.5时大部分表达消失。重要的是，正常和突变胚胎中表达AP - 2α的心脏神经嵴的分布似乎是相同的。通过这项分析，我们提出AP - 2α基因在神经嵴谱系中发挥作用，AP - 2α不是神经嵴细胞迁移所必需的，并且在E11.5之前需要正常的AP - 2α基因功能。AP - 2α可能参与神经嵴与咽下部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。
