Xenopus laevis macrophage migration inhibitory factor is essential for axis formation and neural development
Xenopus laevis macrophage migration inhibitory factor is essential for axis formation and neural development
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DOI：
10.1074/jbc.m311416200
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发表时间：
2004-05-14
影响因子：
4.8
通讯作者：
Ishibashi, T
中科院分区：
文献类型：
--
作者：
Suzuki, M;Takamura, Y;Ishibashi, T
巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）是一种参与后天免疫和先天免疫的免疫调节因子。MIF在免疫系统外也有许多功能，如异构酶和氧化还原酶活性以及控制细胞增殖。考虑到MIF参与各种细胞内和细胞外事件，我们预计MIF可能在脊椎动物发育中也很重要。为了阐明MIF在发育过程中的可能作用，我们利用MIF特异性morpholino oligomers （MOs）敲除非洲爪蟾胚胎中的MIF。为了合成MIF，我们克隆了一个与MIF同源的爪蟾cDNA。序列分析、异构酶活性测定和x射线晶体学分析表明，该cDNA编码的蛋白与哺乳动物的MIF同源。我们对MIF mRNA进行全载原位杂交，发现MIF在正常胚胎的神经组织中有高水平表达。虽然注射了mo的胚胎早期胚胎发生正常，直到原肠期，但它们的神经发育完全被抑制。在尾芽期，注射mo的胚胎缺乏神经和中胚层组织，头部和尾部结构也出现严重缺陷。因此，MIF对爪蟾胚胎轴的形成和神经发育至关重要。
Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine involved in both acquired and innate immunity. MIF also has many functions outside the immune system, such as isomerase and oxidoreductase activities and control of cell proliferation. Considering the involvement of MIF in various intra- and extracellular events, we expected that MIF might also be important in vertebrate development. To elucidate the possible role of MIF in developmental processes, we knocked down MIF in embryos of the African clawed frog Xenopus laevis, using MIF-specific morpholino oligomers (MOs). For the synthesis of the MOs, we cloned a cDNA for a Xenopus homolog of MIF. Sequence analysis, determination of the isomerase activity, and x-ray crystallographic analysis revealed that the protein encoded by the cDNA was the ortholog of mammalian MIF. We carried out whole mount in situ hybridization of MIF mRNA and found that MIF was expressed at high levels in the neural tissues of normal embryos. Although early embryogenesis of MO-injected embryos proceeded normally until the gastrula stage, their neurulation was completely inhibited. At the tailbud stage, the MO-injected embryos lacked neural and mesodermal tissues, and also showed severe defects in their head and tail structures. Thus, MIF was found to be essential for axis formation and neural development of Xenopus embryos.