Brugmann Samantha A, Goodnough L Henry, Gregorieff Alex, Leucht Philipp, ten Berge Derk, Fuerer Christophe, Clevers Hans, Nusse Roel, Helms Jill A
Department of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA 94305, USA.
Development. 2007 Sep;134(18):3283-95. doi: 10.1242/dev.005132. Epub 2007 Aug 15.
At early stages of development, the faces of vertebrate embryos look remarkably similar, yet within a very short timeframe they adopt species-specific facial characteristics. What are the mechanisms underlying this regional specification of the vertebrate face? Using transgenic Wnt reporter embryos we found a highly conserved pattern of Wnt responsiveness in the developing mouse face that later corresponded to derivatives of the frontonasal and maxillary prominences. We explored the consequences of disrupting Wnt signaling, first using a genetic approach. Mice carrying compound null mutations in the nuclear mediators Lef1 and Tcf4 exhibited radically altered facial features that culminated in a hyperteloric appearance and a foreshortened midface. We also used a biochemical approach to perturb Wnt signaling and found that in utero delivery of a Wnt antagonist, Dkk1, produced similar midfacial malformations. We tested the hypothesis that Wnt signaling is an evolutionarily conserved mechanism controlling facial morphogenesis by determining the pattern of Wnt responsiveness in avian faces, and then by evaluating the consequences of Wnt inhibition in the chick face. Collectively, these data elucidate a new role for Wnt signaling in regional specification of the vertebrate face, and suggest possible mechanisms whereby species-specific facial features are generated.
在发育的早期阶段，脊椎动物胚胎的面部看起来非常相似，但在很短的时间内它们就会呈现出物种特有的面部特征。脊椎动物面部这种区域特化的潜在机制是什么？利用转基因Wnt报告基因胚胎，我们在发育中的小鼠面部发现了一种高度保守的Wnt反应模式，该模式后来与额鼻突和上颌突的衍生物相对应。我们首先采用遗传学方法探究了破坏Wnt信号传导的后果。携带核中介因子Lef1和Tcf4复合无效突变的小鼠表现出面部特征的根本改变，最终导致眼距过宽和中面部缩短。我们还采用生化方法干扰Wnt信号传导，发现子宫内注射Wnt拮抗剂Dkk1会产生类似的中面部畸形。我们通过确定鸟类面部Wnt反应模式，然后评估Wnt抑制对鸡面部的影响，来检验Wnt信号传导是控制面部形态发生的一种进化保守机制这一假说。这些数据共同阐明了Wnt信号传导在脊椎动物面部区域特化中的新作用，并提出了产生物种特有的面部特征的可能机制。
