Chicken transcription factor AP-2: cloning, expression and its role in outgrowth of facial prominences and limb buds.
Chicken transcription factor AP-2: cloning, expression and its role in outgrowth of facial prominences and limb buds.
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DOI：
10.1006/dbio.1997.8617
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发表时间：
1997-08
影响因子：
2.7
通讯作者：
Hua Shen;Todd A. Wilke;A. Ashique;M. Narvey;T. Zerucha;E. Savino;T. Williams;J. Richman
中科院分区：
文献类型：
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作者：
Hua Shen;Todd A. Wilke;A. Ashique;M. Narvey;T. Zerucha;E. Savino;T. Williams;J. Richman
鸡胚的胚胎面部发育涉及控制喙的差异生长和图案的基因的顺序激活。在目前的研究中，我们分离了一个这样的基因，转录因子AP-2，已知在小鼠胚胎的面部表达。鸡AP-2α蛋白序列与人和小鼠AP-2蛋白序列有94%的同源性。与鸡AP-2探针的Wholemount原位杂交鉴定了从原始条纹阶段到阶段28的表达。在头部最显著的表达模式是在神经脊细胞迁移期间，当AP-2转录本紧跟先前定位的神经脊细胞束时。随后，面部间充质中的表达在额鼻肿块和侧鼻隆起中最强，在上颌隆起和下颌隆起中表达下调。一旦可见肢芽，在远端间充质中可见高表达，但在顶端外胚脊中不表达。AP-2在第20期胚胎中的表达模式表明，该基因可能在面部隆起和肢芽的“萌发”过程中起重要作用。我们将维甲酸浸泡的珠子植入第20期胚胎的右侧鼻窝，结果特异性地抑制了额鼻部肿块和鼻侧隆起的生长。在给药后8小时内，鼻侧鼻腔AP-2的表达完全下调。此外，维甲酸治疗后，额鼻肿块中AP-2的正常上调没有发生。伴随着AP-2的下调，右侧鼻窝周围的程序性细胞死亡增加。其形态发生不受维甲酸影响的突起没有改变表达模式。我们在第20期肢芽中去除顶端外胚层的脊状突起，发现AP-2的表达在去除脊状突起4小时后部分下调，在剥离8小时后完全下调。将浸泡成纤维细胞生长因子-4的珠子应用于肢芽顶端，可维持AP-2的表达。因此，AP-2参与发育，并可能受到面部和肢体外胚层中存在的FGFs等因素的调节。
Embryonic facial development in chick embryos involves a sequential activation of genes that control differential growth and patterning of the beak. In the present study we isolate one such gene, the transcription factor, AP-2, that is known to be expressed in the face of mouse embryos. The protein sequence of chick AP-2alpha is 94% homologous to human and mouse AP-2. Wholemount in situ hybridization with a probe for chick AP-2 identifies expression from primitive streak stages up to stage 28. The most striking expression patterns in the head are during neural crest cell migration when AP-2 transcripts follow closely the tracts previously mapped for neural crest cells. Later, expression in the facial mesenchyme is strongest in the frontonasal mass and lateral nasal prominences and is downregulated in the maxillary and mandibular prominences. Once limb buds are visible, high expression is seen in the distal mesenchyme but not in the apical ectodermal ridge. The expression patterns of AP-2 in stage 20 embryos suggested that the gene may be important in "budding out" of facial prominences and limb buds. We implanted beads soaked in retinoic acid in the right nasal pit of stage 20 embryos resulting in a specific inhibition of outgrowth of the frontonasal mass and lateral nasal prominences. AP-2 expression was completely down-regulated in the lateral nasal within 8 hr of bead application. In addition, the normal up-regulation of AP-2 in the frontonasal mass did not occur following retinoic-acid treatment. There was an increase in programmed cell death around the right nasal pit that accompanied the down-regulation of AP-2. Prominences whose morphogenesis were not affected by retinoic acid did not have altered expression patterns. We removed the apical ectodermal ridge in stage 20 limb buds and found that AP-2 expression was partially downregulated 4 hr following ridge removal and completely downregulated 8 hr following stripping. Application of an FGF-4 soaked bead to the apex of the limb bud maintained AP-2 expression. Thus AP-2 is involved in outgrowth and could be regulated by factors such as FGFs that are present in the ectoderm of both the face and limb.