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Abstract：
The evolution of jaws has played a major role in the success of vertebrate expansion into a wide variety of ecological niches. A fundamental, yet unresolved, question in craniofacial biology is about the origin of the premaxilla, the most distal bone present in the upper jaw of all amniotes. Recent reports have suggested that the mammalian premaxilla is derived from embryonic maxillary prominences rather than the frontonasal ectomesenchyme as previously shown in studies of chicken embryos. However, whether mammalian embryonic frontonasal ectomesenchyme contributes to the premaxillary bone has not been investigated and a tool to trace the contributions of the frontonasal ectomesenchyme to facial structures in mammals is lacking. The expression of the Alx3 gene is activated highly specifically in the frontonasal ectomesenchyme, but not in the maxillary mesenchyme, from the beginning of facial morphogenesis in mice. Here, we report the generation and characterization of a novel Alx3CreERT2 knock-in mouse line that express tamoxifen-inducible Cre DNA recombinase from the Alx3 locus. Tamoxifen treatment of Alx3CreERT2/+;Rosa26mTmG/+ embryos at E7.5, E8.5, E9.5, and E10.5, each induced specific labeling of the embryonic medial nasal and lateral nasal mesenchyme but not the maxillary mesenchyme. Lineage tracing of Alx3CreERT2-labeled frontonasal mesenchyme from E9.5 to E16.5 clearly showed that the frontonasal mesenchyme cells give rise to the osteoblasts generating the premaxillary bone. Furthermore, we characterize a Dlx1-Cre BAC transgenic mouse line that expresses Cre activity in the embryonic maxillary but not the frontonasal mesenchyme and show that the Dlx1-Cre labeled embryonic maxillary mesenchyme cells contribute to the maxillary bone as well as the soft tissues lateral to both the premaxillary and maxillary bones but not to the premaxillary bone. These results clearly demonstrate the developmental origin of the premaxillary bone from embryonic frontonasal ectomesenchyme cells in mice and confirm the evolutionary homology of the premaxilla across amniotes.
摘要：
颌骨的进化在脊椎动物向各种生态位扩张的成功中发挥了重要作用。一个基本的，尚未解决，颅面生物学中的问题是关于前颌骨的起源，所有羊膜的上颌中存在的最远端骨。最近的报道表明，哺乳动物的前颌骨源自胚胎上颌骨突出，而不是先前在鸡胚胎研究中显示的额鼻外充质。然而,尚未研究哺乳动物胚胎额鼻外植体是否有助于上颌前骨，并且缺乏追踪额鼻外植体对哺乳动物面部结构的贡献的工具。Alx3基因的表达在额鼻外胚中被高度特异性激活，但不是在上颌间质,从小鼠面部形态发生开始。这里,我们报告了从Alx3基因座表达他莫昔芬诱导的CreDNA重组酶的新型Alx3CreERT2敲入小鼠系的产生和表征。他莫昔芬治疗Alx3CreERT2/；Rosa26mTmG/E7.5，E8.5，E9.5和E10.5的胚胎均诱导了胚胎内侧鼻和外侧鼻间质的特定标记，但上颌间质却没有。从E9.5到E16.5的Alx3CreERT2标记的额鼻间充质的谱系追踪清楚地表明，额鼻间充质细胞产生成骨细胞，从而产生上颌前骨。此外，我们表征了Dlx1-CreBAC转基因小鼠系，该小鼠系在胚胎上颌而不是额鼻间充质中表达Cre活性，并表明Dlx1-Cre标记的胚胎上颌间充质细胞有助于上颌骨以及上颌前骨和上颌骨外侧的软组织，但不有助于上颌骨。这些结果清楚地证明了小鼠胚胎额鼻外充质细胞的上颌前骨的发育起源，并证实了上颌骨在羊膜中的进化同源性。
