Pöpperl H, Schmidt C, Wilson V, Hume C R, Dodd J, Krumlauf R, Beddington R S
Laboratory of Developmental Neurobiology, MRC National Institute for Medical Research, Mill Hill, London, UK.
Development. 1997 Aug;124(15):2997-3005. doi: 10.1242/dev.124.15.2997.
Transgenic embryos expressing Cwnt8C under the control of the human beta-actin promoter exhibit duplicated axes or a severely dorsalised phenotype. Although the transgene was introduced into fertilised eggs all duplications occurred within a single amnion and, therefore, arose from the production of more than one primitive streak at the time of gastrulation. Morphological examination and the expression of diagnostic markers in transgenic embryos suggested that ectopic Cwnt8C expression produced only incomplete axis duplication: axes were always fused anteriorly, there was a reduction in tissue rostral to the anterior limit of the notochord, and no duplicated expression domain of the forebrain marker Hesx1 was observed. Anterior truncations were evident in dorsalised transgenic embryos containing a single axis. These results are discussed in the light of the effects of ectopic Xwnt8 in Xenopus embryos, where its early expression leads to complete axis duplication but expression after the mid-blastula transition causes anterior truncation. It is proposed that while ectopic Cwnt8C in the mouse embryo can duplicate the primitive streak and node this only produces incomplete axis duplication because specification of the anterior aspect of the axis, as opposed to maintenance of anterior character, is established by interaction with anterior primitive endoderm rather than primitive streak derivatives.
在人类β-肌动蛋白启动子控制下表达Cwnt8C的转基因胚胎表现出轴重复或严重的背化表型。尽管转基因被导入受精卵中，但所有的重复都发生在单个羊膜内，因此，是在原肠胚形成时由不止一条原条的产生引起的。对转基因胚胎的形态学检查和诊断标志物的表达表明，异位Cwnt8C表达仅产生不完全的轴重复：轴总是在前部融合，脊索前部界限前方的组织减少，并且未观察到前脑标志物Hesx1的重复表达结构域。在含有单轴的背化转基因胚胎中，前部截断很明显。根据非洲爪蟾胚胎中异位Xwnt8的作用对这些结果进行了讨论，在非洲爪蟾胚胎中，其早期表达导致完全的轴重复，但在囊胚中期转换后表达则导致前部截断。有人提出，虽然小鼠胚胎中的异位Cwnt8C可以使原条和节点重复，但这只会产生不完全的轴重复，因为轴前部的特化，与前部特征的维持相反，是通过与前部原始内胚层而非原条衍生物的相互作用建立的。
