Zhou X, Sasaki H, Lowe L, Hogan B L, Kuehn M R
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Nature. 1993 Feb 11;361(6412):543-7. doi: 10.1038/361543a0.
During gastrulation, the three germ layers of the embryo are formed and organized along the anterior-posterior body axis. In the mouse, gastrulation involves the delamination of ectodermal cells through the primitive streak and their differentiation into mesoderm. These processes do not occur in embryos homozygous for a retrovirally induced recessive prenatal lethal mutation, the strain 413-d insertional mutation. Instead of giving rise to mesoderm, embryonic ectoderm in 413-d mutants overproliferates and then rapidly degenerates, although extraembryonic lineages remain viable. Here we isolate a candidate for the mutated gene which encodes a new member of the transforming growth factor-beta (TGF-beta) superfamily. Expression is first detected in primitive streak-stage embryos at about the time of mesoderm formation. It then becomes highly localized in the node at the anterior of the primitive streak. This region is analogous to chick Hensen's node and Xenopus dorsal lip (Spemann's organizer), which can induce secondary body axes when grafted into host embryos (reviewed in refs 5 and 6). Our findings suggest that this gene, named nodal, encodes a signalling molecule essential for mesoderm formation and subsequent organization of axial structures in early mouse development.
在原肠胚形成过程中,胚胎的三个胚层沿前后体轴形成并组织起来。在小鼠中,原肠胚形成涉及外胚层细胞通过原条分层并分化为中胚层。这些过程在一种逆转录病毒诱导的隐性产前致死突变(413 - d插入突变品系)的纯合胚胎中不会发生。在413 - d突变体中,胚胎外胚层不是产生中胚层,而是过度增殖,然后迅速退化,尽管胚外谱系仍然存活。在这里,我们分离出了一个突变基因的候选基因,它编码转化生长因子 - β(TGF - β)超家族的一个新成员。该基因的表达最初在原条形成阶段的胚胎中检测到,大约在中胚层形成时。然后它高度定位于原条前端的节点。这个区域类似于鸡的亨氏节和非洲爪蟾的背唇(施佩曼组织者),当移植到宿主胚胎中时可以诱导次生体轴(参考文献5和6中有综述)。我们的研究结果表明,这个名为节点(Nodal)的基因编码一种信号分子,对小鼠早期发育中中胚层的形成和随后的轴向结构组织至关重要。