The first branchial arch (BA1), which is derived from cranial neural crest (CNC) cells, gives rise to various orofacial tissues. Cre mice are widely used for the determination of CNC and exploration of gene functions in orofacial development. However, there is a lack of Cre mice specifically marked BA1’s cells. Pax2-Cre allele was previously generated and has been widely used in the field of inner ear development. Here, by compounding Pax2-Cre and R26R-mTmG mice, we found a specific expression pattern of Pax2⁺ cells that marked BA1’s mesenchymal cells and the BA1-derivatives. Compared to Pax2-Cre; R26R-mTmG allele, GFP⁺ cells were abundantly found both in BA1 and second branchial arch in Wnt1-Cre;R26R-mTmG mice. As BMP4 signaling is required for orofacial development, we over-activated Bmp4 by using Pax2-Cre; pMes-BMP4 strain. Interestingly, our results showed bilateral hyperplasia between the upper and lower teeth. We also compare the phenotypes of Wnt1-Cre; pMes-BMP4 and Pax2-Cre; pMes-BMP4 strains and found severe deformation of molar buds, palate, and maxilla-mandibular bony structures in Wnt1-Cre; pMes-BMP4 mice; however, the morphology of these orofacial organs were comparable between controls and Pax2-Cre; pMes-BMP4 mice except for bilateral hyperplastic tissues. We further explore the properties of the hyperplastic tissue and found it is not derived from Runx2⁺ cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8. In sum, our findings suggest altering BMP4 signaling in BA1-specific cell lineage may lead to unique phenotypes in orofacial regions, further hinting that Pax2-Cre mice could be a new model for genetic manipulation of BA1-derived organogenesis in the orofacial region.

第一鳃弓 (BA1) 源自颅神经嵴 (CNC) 细胞，产生各种口面部组织。Cre 小鼠广泛用于 CNC 的测定和口面部发育中基因功能的探索。然而，目前缺乏特异性标记BA1细胞的Cre小鼠。Pax2 -Cre 等位基因先前已生成并已广泛应用于内耳发育领域。在这里，通过复合Pax2 -Cre 和R26R- mTmG 小鼠，我们发现了Pax2 ⁺细胞的特定表达模式，该模式标记了 BA1 的间充质细胞和 BA1 衍生物。与Pax2 -Cre相比；R26R -mTmG 等位基因，GFP ⁺在Wnt1 -Cre的 BA1 和第二鳃弓中均发现大量细胞；R26R -mTmG 小鼠。由于口面部发育需要 BMP4 信号，我们通过使用Pax2 -Cre 过度激活了Bmp4；pMes -BMP4 菌株。有趣的是，我们的结果显示上下牙之间存在双侧增生。我们还比较了Wnt1 -Cre的表型；pMes -BMP4 和Pax2 -Cre；pMes -BMP4 菌株并发现Wnt1 -Cre中的磨牙芽、上颚和上颌骨-下颌骨结构严重变形；时间点-BMP4小鼠；然而，这些口面部器官的形态在对照组和Pax2 -Cre 之间具有可比性；pMes -BMP4 小鼠，双侧增生组织除外。我们进一步探索增生组织的特性，发现它不是来源于Runx2 ⁺细胞而是表达Msx1，可能是由于细胞增殖异常和p-Smad1/5/8表达模式改变所致。总之，我们的研究结果表明，改变 BA1 特异性细胞谱系中的 BMP4 信号可能导致口面部区域的独特表型，进一步暗示Pax2 -Cre 小鼠可能是口面部区域 BA1 衍生器官发生基因操作的新模型。