通过产生音猬因子的细胞诱导鸡下颌间充质中镜像多余颌骨的形成。
Induction of mirror-image supernumerary jaws in chicken mandibular mesenchyme by Sonic Hedgehog-producing cells.
作者信息
Brito José M, Teillet Marie-Aimée, Le Douarin Nicole M
机构信息
CNRS, UPR 2197, Laboratoire de Développement, Evolution et Plasticité du Système nerveux, Institut de Neurobiologie Alfred Fessard, F-91198 Gif-sur-Yvette, France.
出版信息
Development. 2008 Jul;135(13):2311-9. doi: 10.1242/dev.019125.
Previous studies have shown that Sonic Hedgehog (Shh) signaling is crucial for the development of the first branchial arch (BA1) into a lower-jaw in avian and mammalian embryos. We have already shown that if Shh expression is precociously inhibited in pharyngeal endoderm, neural crest cells migrate to BA1 but fail to survive, and Meckel's cartilage and associated structures do not develop. This phenotype can be rescued by addition of an exogenous source of Shh. To decipher the role of Shh, we explored the consequences of providing an extra source of Shh to the presumptive BA1 territory. Grafting quail fibroblasts engineered to produce Shh (QT6-Shh), at the 5- to 8-somite stage, resulted in the induction of mirror-image extra lower jaws, caudolateral to the normal one. It turns out that the oral opening epithelium, in which Shh, Fgf8 and Bmp4 are expressed in a definite pattern, functions as an organizing center for lower-jaw development. In our experimental design, the extra source of Shh activates Fgf8, Bmp4 and Shh genes in caudal BA1 ectoderm in a spatial pattern similar to that of the oral epithelium, and regularly leads to the formation of two extra lower-jaw-organizing centers with opposite rostrocaudal polarities. These results emphasize the similarities between the developmental processes of the limb and mandibular buds, and show that in both cases Shh-producing cells create a zone of polarizing activity for the structures deriving from them.
先前的研究表明,在鸟类和哺乳动物胚胎中,音猬因子(Shh)信号通路对于第一鳃弓(BA1)发育成下颌至关重要。我们已经表明,如果在咽内胚层中过早抑制Shh表达,神经嵴细胞会迁移至BA1,但无法存活,并且Meckel软骨及相关结构无法发育。添加外源性Shh可挽救此表型。为了解析Shh的作用,我们探究了向假定的BA1区域提供额外Shh来源的后果。在5至8体节期移植经基因工程改造以产生Shh的鹌鹑成纤维细胞(QT6-Shh),导致在正常下颌的后外侧诱导出镜像额外下颌。结果表明,Shh、Fgf8和Bmp4以特定模式表达的口裂上皮,作为下颌发育的组织中心发挥作用。在我们的实验设计中,额外的Shh来源以与口腔上皮相似的空间模式激活尾侧BA1外胚层中的Fgf8、Bmp4和Shh基因,并经常导致形成两个具有相反头尾极性的额外下颌组织中心。这些结果强调了肢体和下颌芽发育过程之间的相似性,并表明在这两种情况下,产生Shh的细胞都会为源自它们的结构创建一个极化活性区域。