Muraoka O, Ichikawa H, Shi H, Okumura S, Taira E, Higuchi H, Hirano T, Hibi M, Miki N
Department of Pharmacology, Division of Molecular Oncology, Department of Oncology, Biomedical Research Center, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Dev Biol. 2000 Dec 1;228(1):29-40. doi: 10.1006/dbio.2000.9909.
Kheper is a novel member of the ZFH (zinc-finger and homeodomain protein)/deltaEF1 family in zebrafish. kheper transcripts are first detected in the epiblast of the dorsal blastoderm margin at the early gastrula stage and kheper is expressed in nearly all the neuroectoderm at later stages. kheper expression was expanded in noggin RNA-injected embryos and also in swirl mutant embryos and was reduced in bmp4 RNA-injected embryos and chordino mutant embryos, suggesting that kheper acts downstream of the neural inducers Noggin and Chordino. Overexpression of Kheper elicited ectopic expansion of the neuroectoderm-specific genes fkd3, hoxa-1, and eng3, and the ectopic expression of hoxa-1 was not inhibited by BMP4 overexpression. Kheper interacted with the transcriptional corepressors CtBP1 and CtBP2. Overexpression of a Kheper mutant lacking the homeodomain or of a VP16-Kheper fusion protein disturbed the development of the neuroectoderm and head structures. These data underscore the role of Kheper in the development of the neuroectoderm and indicate that Kheper acts as a transcriptional repressor.
Kheper是斑马鱼中ZFH(锌指和同源结构域蛋白)/deltaEF1家族的一个新成员。在原肠胚早期,kheper转录本首先在背侧胚盘边缘的上胚层中被检测到,在后期,kheper在几乎所有神经外胚层中表达。kheper的表达在注射noggin RNA的胚胎以及swirl突变体胚胎中有所扩展,而在注射bmp4 RNA的胚胎和chordino突变体胚胎中则减少,这表明kheper在神经诱导因子Noggin和Chordino的下游起作用。Kheper的过表达引发了神经外胚层特异性基因fkd3、hoxa-1和eng3的异位扩展,并且hoxa-1的异位表达不受BMP4过表达的抑制。Kheper与转录共抑制因子CtBP1和CtBP2相互作用。缺乏同源结构域的Kheper突变体或VP16-Kheper融合蛋白的过表达扰乱了神经外胚层和头部结构的发育。这些数据强调了Kheper在神经外胚层发育中的作用,并表明Kheper作为一种转录抑制因子发挥作用。