Ding J, Yang L, Yan Y T, Chen A, Desai N, Wynshaw-Boris A, Shen M M
Center for Advanced Biotechnology and Medicine and Dept of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Nature. 1998 Oct 15;395(6703):702-7. doi: 10.1038/27215.
The anterior-posterior axis of the mouse embryo is established by two distinct organizing centres in the anterior visceral endoderm and the distal primitive streak. These organizers induce and pattern the head and trunk respectively, and have been proposed to be localized through coordinate cell movements that rotate a pre-existing proximal-distal axis. Here we show that correct localization of both head- and trunk-organizing centres requires Cripto, a putative signalling molecule that is a member of the EGF-CFC gene family. Before gastrulation, Cripto is asymmetrically expressed in a proximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm. A Cripto null mutation generated by targeted gene disruption results in homozygous Cripto-/- embryos that mostly consist of anterior neuroectoderm and lack posterior structures, thus resembling a head without a trunk. Notably, markers of the head organizer are located at the distal end of the embryo, whereas markers of the primitive streak are absent or localized to the proximal side. Our results indicate that Cripto signalling is essential for the conversion of a proximal-distal asymmetry into an orthogonal anterior-posterior axis.
小鼠胚胎的前后轴由前内脏内胚层和远端原始条带中的两个不同的组织中心建立。这些组织者分别诱导头部和躯干的形成并决定其模式，并且有人提出它们是通过协调细胞运动来定位的，这些运动旋转预先存在的近端 - 远端轴。在这里，我们表明头部和躯干组织中心的正确定位需要Cripto，一种推定的信号分子，它是EGF - CFC基因家族的成员。在原肠胚形成之前，Cripto在胚泡中以近端 - 远端梯度不对称表达，随后在原始条带和新形成的胚胎中胚层中表达。通过靶向基因破坏产生的Cripto无效突变导致纯合的Cripto - / - 胚胎，这些胚胎主要由前神经外胚层组成且缺乏后部结构，因此类似于没有躯干的头部。值得注意的是，头部组织者的标志物位于胚胎的远端，而原始条带的标志物不存在或定位在近端。我们的结果表明，Cripto信号传导对于将近端 - 远端不对称转化为正交的前后轴至关重要。
