Agathon Antoine, Thisse Christine, Thisse Bernard
Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, CNRS/INSERM/ULP, 1 rue Laurent Fries, BP10142, CU de Strasbourg, 67404 Illkirch Cedex, France.
Nature. 2003 Jul 24;424(6947):448-52. doi: 10.1038/nature01822.
Based on grafting experiments, Mangold and Spemann showed the dorsal blastopore lip of an amphibian gastrula to be able to induce a secondary body axis. The equivalent of this organizer region has been identified in different vertebrates including teleosts. However, whereas the graft can induce ectopic head and trunk, endogenous and ectopic axes fuse in the posterior part of the body, raising the question of whether a distinct organizer region is necessary for tail development. Here we reveal, by isochronic and heterochronic transplantation, the existence of a tail organizer deriving from the ventral margin of the zebrafish embryo, which is independent of the dorsal Spemann organizer. Loss-of-function experiments reveal that bone morphogenetic protein (BMP), Nodal and Wnt8 signalling pathways are required for tail development. Moreover, stimulation of naive cells by a combination of BMP, Nodal and Wnt8 mimics the tail-organizing activity of the ventral margin and induces surrounding tissues to become tail. In contrast to induction of the vertebrate head, known to result from the triple inhibition of BMP, Nodal and Wnt, here we show that induction of the tail results from the triple stimulation of BMP, Nodal and Wnt8 signalling pathways.
基于移植实验，曼戈尔德和施佩曼发现两栖类原肠胚的背侧胚孔唇能够诱导形成次生体轴。在包括硬骨鱼在内的不同脊椎动物中都已鉴定出该组织者区域的等效物。然而，尽管移植能够诱导异位的头部和躯干形成，但内源性和异位轴在身体后部融合，这就引发了一个问题，即尾巴发育是否需要一个独特的组织者区域。在这里，我们通过等时和异时移植揭示，斑马鱼胚胎腹侧边缘存在一个独立于背侧施佩曼组织者的尾巴组织者。功能丧失实验表明，骨形态发生蛋白（BMP）、Nodal和Wnt8信号通路是尾巴发育所必需的。此外，用BMP、Nodal和Wnt8组合刺激未分化细胞可模拟腹侧边缘的尾巴组织活性，并诱导周围组织形成尾巴。与已知由BMP、Nodal和Wnt的三重抑制导致的脊椎动物头部诱导不同，我们在此表明，尾巴的诱导是由BMP、Nodal和Wnt8信号通路的三重刺激引起的。
