Suri Crystal, Haremaki Tomomi, Weinstein Daniel C
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Dev Biol. 2004 Jan 1;265(1):90-104. doi: 10.1016/j.ydbio.2003.09.017.
The winged-helix transcription factor HNF3beta/FoxA2 is expressed in embryonic organizing centers of the gastrulating mouse, frog, fish, and chick. In the mouse, HNF3beta is required for the formation of the mammalian node and notochord, and can induce ectopic floor plate formation when misexpressed in the developing neural tube; HNF3beta expression in the extraembryonic endoderm is also necessary for the proper morphogenesis of the mammalian primitive streak. In the frog Xenopus laevis, several lines of evidence suggest that the related winged-helix factor Pintallavis functions as the ortholog of mammalian HNF3beta in both axial mesoderm and neurectoderm; the role of Xenopus HNF3beta itself, however, has not been clearly defined, and is the subject of this study. HNF3beta is widely expressed in the vegetal pole but, as previously suggested, is excluded from the gastrula-stage mesoderm. We find that expression of an HNF3beta-Engrailed repressor fusion protein induces ectopic axes and inhibits head formation in Xenopus embryos, while ectopic HNF3beta inhibits mesoderm and anterior endoderm formation in explant assays and in vivo. Our studies suggest that HNF3beta target genes function to limit the extent of mesoderm formation in the Xenopus gastrula, and point to related roles for Xenopus HNF3beta and the extraembryonic component of mammalian HNF3beta during vertebrate gastrulation.
翼状螺旋转录因子HNF3β/FoxA2在原肠胚形成期的小鼠、蛙、鱼和鸡的胚胎组织中心表达。在小鼠中，HNF3β是哺乳动物节点和脊索形成所必需的，并且在发育中的神经管中错误表达时可诱导异位底板形成；HNF3β在胚外内胚层中的表达对于哺乳动物原条的正常形态发生也是必需的。在非洲爪蟾中，几条证据表明相关的翼状螺旋因子Pintallavis在轴中胚层和神经外胚层中作为哺乳动物HNF3β的直系同源物发挥作用；然而，非洲爪蟾HNF3β本身的作用尚未明确界定，本研究将探讨这一问题。HNF3β在植物极广泛表达，但如先前所述，在原肠胚期的中胚层中不表达。我们发现，HNF3β-Engrailed阻遏物融合蛋白的表达可诱导非洲爪蟾胚胎形成异位轴并抑制头部形成，而异位HNF3β在体外实验和体内均可抑制中胚层和前端内胚层的形成。我们的研究表明，HNF3β靶基因的功能是限制非洲爪蟾原肠胚中胚层形成的范围，并指出非洲爪蟾HNF3β和哺乳动物HNF3β的胚外成分在脊椎动物原肠胚形成过程中的相关作用。
