Laboratory for Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima Minamimachi, Chuou-ku, Kobe 650-0047, Japan.
Dev Biol. 2010 Jun 1;342(1):110-20. doi: 10.1016/j.ydbio.2010.03.013. Epub 2010 Mar 29.
In the mouse, the Otx2 gene has been shown to play essential roles in the visceral endoderm during anterior-posterior axis formation and head induction. While these are primary processes in vertebrate embryogenesis, the visceral endoderm is a tissue unique to mammals. Two enhancers (VE and CM) have been previously found to direct Otx2 expression during early embryogenesis. This study demonstrates that in anterior visceral endoderm the CM enhancer does not have an activity by itself, but enhances the activity of the VE enhancer. These two enhancers also cooperate for the activities in anterior mesendoderm and cephalic mesenchyme. Comparative studies suggest that VE enhancer function was most likely established before the divergence of sarcopterygians into Actinistia, Dipnoi and tetrapods, while the nucleotide sequence corresponding to the VE enhancer was already present in the last common ancestor of bony fishes. The CM enhancer sequence and function would have been also established in ancestral sarcopterygians. The VE/CM enhancers and their gene cascades in the ancestral sarcopterygian head organizer would then have been co-opted by amphibian deep endoderm cells and mammalian visceral endoderm cells for the head development.
在老鼠中，Otx2 基因已被证明在前后轴形成和头部诱导过程中对内脏内胚层发挥重要作用。虽然这些是脊椎动物胚胎发生中的主要过程，但内脏内胚层是哺乳动物所特有的组织。先前已经发现两个增强子（VE 和 CM）在早期胚胎发生中指导 Otx2 的表达。本研究表明，在前内脏内胚层中，CM 增强子本身没有活性，但增强了 VE 增强子的活性。这两个增强子在前中胚层和头间充质中也具有协同作用。比较研究表明，VE 增强子的功能很可能在肉鳍鱼分化为总鳍鱼、两栖动物和四足动物之前就已经确立，而与 VE 增强子相对应的核苷酸序列已经存在于硬骨鱼的最后共同祖先中。CM 增强子序列和功能也可能在祖先肉鳍鱼中建立。然后，祖先后鳍鱼头部组织者中的 VE/CM 增强子及其基因级联被两栖动物深部内胚层细胞和哺乳动物内脏内胚层细胞共同用于头部发育。
