Ohta Kunimasa, Lupo Giuseppe, Kuriyama Sei, Keynes Roger, Holt Christine E, Harris William A, Tanaka Hideaki, Ohnuma Shin-Ichi
Department of Developmental Neurobiology Graduate School of Medical Sciences.
PRESTO, JST 4-1-8 Honcho Kawaguchi Saitama 332-0012 Japan.
Dev Cell. 2004 Sep;7(3):347-358. doi: 10.1016/j.devcel.2004.08.014.
During chick gastrulation, inhibition of BMP signaling is required for primitive streak formation and induction of Hensen's node. We have identified a unique secreted protein, Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family and is expressed in the primitive streak and Hensen's node. Grafts of cells expressing TSK in combination with the middle primitive streak induce an ectopic Hensen's node, while electroporation of TSK siRNA inhibits induction of the node. In Xenopus embryos, TSK can block BMP function and induce a secondary dorsal axis, while it can dorsalize ventral mesoderm and induce neural tissue in embryonic explants. Biochemical analysis shows that TSK binds directly to both BMP and chordin and forms a ternary complex with them. These observations indicate that TSK is an essential dorsalizing factor involved in the induction of Hensen's node.
在鸡胚原肠胚形成过程中,BMP信号的抑制对于原条的形成和亨氏结的诱导是必需的。我们鉴定出一种独特的分泌蛋白,筑丝蛋白(TSK),它属于富含亮氨酸小分子蛋白聚糖(SLRP)家族,在原条和亨氏结中表达。表达TSK的细胞与中胚层原条结合移植可诱导异位亨氏结,而TSK小干扰RNA的电穿孔则抑制结的诱导。在非洲爪蟾胚胎中,TSK可阻断BMP功能并诱导形成第二背轴,同时它可使腹侧中胚层背化并在胚胎外植体中诱导神经组织形成。生化分析表明,TSK直接与BMP和脊索蛋白结合并与它们形成三元复合物。这些观察结果表明,TSK是参与亨氏结诱导的一种重要的背化因子。