Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo
Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo
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作者：
Ding, JX;Yang, L;Shen, MM
小鼠胚胎的前后轴由两个不同的组织中心建立，分别位于前内脏内胚层和远端原始条纹（1-7）。这些组织者分别诱导和塑造了头部和躯干，并被认为是通过旋转已有的近端-远端轴的坐标细胞运动来定位的（6,8）。在这里，我们发现头部和躯干组织中心的正确定位都需要Cripto(9,10)，这是一种假定的信号分子，是EGF-CFC基因家族的成员（11,12）。在原肠胚形成之前，Cripto在外胚层中以近端-远端梯度不对称表达，随后在原始条纹和新形成的胚胎中表达。由靶向基因破坏产生的Cripto null突变导致纯合子Cripto（-/-）胚胎主要由前神经外胚层组成，缺乏后部结构，因此类似于没有躯干的头。值得注意的是，头部组织者的标记位于胚胎的远端，而原始条纹的标记则缺失或定位于近端。我们的研究结果表明，加密信号对于一个pro的转换是必不可少的；近端和远端不对称形成一个正交的前后轴。
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(1-7). 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 pre-existing proximal-distal axis(6,8). Here we show that correct localization of both head- and trunk-organizing centres requires Cripto(9,10), a putative signalling molecule that is a member of the EGF-CFC gene family(11,12), 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 pro;proximal-distal asymmetry into an orthogonal anterior-posterior axis.