Biben C, Stanley E, Fabri L, Kotecha S, Rhinn M, Drinkwater C, Lah M, Wang C C, Nash A, Hilton D, Ang S L, Mohun T, Harvey R P
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Dev Biol. 1998 Feb 15;194(2):135-51. doi: 10.1006/dbio.1997.8812.
Xenopus cerberus (Xcer) is a cytokine expressed in anterior mesendoderm overlapping and surrounding Spemann's gastrula organiser. When misexpressed in blastomeres, Xcer can induce ectopic heads with well-defined brain, cement gland, olfactory placodes, cyclopic eye, and occasionally liver and heart. We report here the identification of mCer-1, a murine gene related to cerberus. Both mCer-1 and Xcer appear to belong to the cystine knot superfamily, which includes TGF beta s and BMPs. In Xenopus animal cap assays, mCer-1 and Xcer induced cement glands and markers of anterior neural tissue and endoderm, characteristic of BMP inhibition. Furthermore, both antagonised the ventrolateral mesoderm-inducing activity of coexpressed BMP4. In mouse embryos, mCer-1 was expressed at early gastrulation in a stripe of primitive endoderm along the future anterior side of the egg cylinder, a region essential for anterior patterning. A second phase of expression was detected in anterior embryonic mesendoderm, and by late-streak stages most of the anterior half of the embryo was positive, except for the node and cardiac progenitors. Expression was later seen in the cranial portion of the two most-recently formed somites and in two stripes within presomitic mesoderm. In embryos lacking Otx2, a homeogene with a demonstrated role in anterior patterning, mCer-1 was still expressed in an anterior zone, although often abnormally. The data suggest that mCer-1 shares structural, functional, and expression characteristics with Xcer and may participate in patterning the anterior of the embryo and nascent somite region, in part, through a BMP-inhibitory mechanism.
非洲爪蟾的“冥河神”基因(Xcer)是一种细胞因子,在前肠内胚层表达,与施佩曼原肠胚组织者重叠并环绕其周围。当在卵裂球中错误表达时,Xcer可诱导出具有明确脑、鼻腺、嗅基板、独眼以及偶尔还有肝脏和心脏的异位头部。我们在此报告小鼠“冥河神”基因-1(mCer-1)的鉴定,它是一种与“冥河神”基因相关的小鼠基因。mCer-1和Xcer似乎都属于胱氨酸结超家族,该家族包括转化生长因子β(TGFβs)和骨形态发生蛋白(BMPs)。在非洲爪蟾动物帽实验中,mCer-1和Xcer诱导出鼻腺以及前神经组织和内胚层的标志物,这是BMP抑制的特征。此外,二者都拮抗共表达的BMP4诱导腹外侧中胚层的活性。在小鼠胚胎中,mCer-1在原肠胚形成早期沿着卵柱未来的前侧在一条原始内胚层条带中表达,该区域对于前部模式形成至关重要。在胚胎前肠内胚层中检测到第二阶段的表达,到原条后期,胚胎前半部分的大部分区域呈阳性,但节点和心脏祖细胞除外。随后在最近形成的两个体节的头部区域以及体节前中胚层内的两条条带中可见表达。在缺乏Otx2(一种在前部模式形成中具有明确作用的同源基因)的胚胎中,mCer-1仍在前部区域表达,尽管通常不正常。数据表明,mCer-1与Xcer具有结构、功能和表达特征,可能部分通过BMP抑制机制参与胚胎前部和新生体节区域的模式形成。