Varlet I, Collignon J, Robertson E J
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Development. 1997 Mar;124(5):1033-44. doi: 10.1242/dev.124.5.1033.
Mouse nodal, a member of the TGFbeta family of secreted growth factors is essential for gastrulation. We recently generated a nodal(lacZ) reporter allele by homologous recombination in ES cells. In the present study, beta-galactosidase staining in the perigastrulation-stage embryo has demonstrated the site of highest nodal expression is localised to the prospective posterior region of the epiblast marking the site of primitive streak formation. We also documented transient nodal.lacZ expression in the visceral endoderm prior to and during early streak formation. A mosaic analysis using wild-type ES cells to rescue nodal-deficient embryos allowed us to document functionally distinct nodal activities in the embryonic ectodermal and primitive endodermal cell lineages. nodal signaling in the ectoderm is necessary for primitive streak formation as the gastrulation defect of nodal-deficient embryos can be rescued by the inclusion of small numbers of wild-type cells. In addition, we show that chimeric embryos composed of nodal-deficient primitive endoderm fail to develop rostral neural structures. Thus we conclude that the action of nodal, a TGFbeta-related growth factor expressed in the primitive endoderm, is critical for patterning of the anterior aspects of the A-P axis.
小鼠Nodal是分泌型生长因子TGFβ家族的一员，对原肠胚形成至关重要。我们最近通过胚胎干细胞中的同源重组产生了一个Nodal（lacZ）报告基因等位基因。在本研究中，原肠胚形成期胚胎中的β-半乳糖苷酶染色表明，Nodal表达最高的部位定位于上胚层的预期后部区域，该区域标志着原条形成的部位。我们还记录了早期原条形成之前及形成过程中在内脏内胚层中短暂的Nodal.lacZ表达。使用野生型胚胎干细胞拯救Nodal缺陷胚胎的嵌合分析使我们能够记录胚胎外胚层和原始内胚层细胞谱系中功能不同的Nodal活性。外胚层中的Nodal信号传导对于原条形成是必需的，因为通过加入少量野生型细胞可以拯救Nodal缺陷胚胎的原肠胚形成缺陷。此外，我们表明由Nodal缺陷的原始内胚层组成的嵌合胚胎无法发育出头部神经结构。因此我们得出结论，原始内胚层中表达的与TGFβ相关的生长因子Nodal的作用对于前后轴前部的模式形成至关重要。
