Sykes T G, Rodaway A R, Walmsley M E, Patient R K
Developmental Biology Research Centre, The Randall Institute, King's College London, London WC2B 5RL, UK.
Development. 1998 Dec;125(23):4595-605. doi: 10.1242/dev.125.23.4595.
In Xenopus, the dorsoventral axis is patterned by the interplay between active signalling in ventral territories, and secreted antagonists from Spemann's organiser. Two signals are important in ventral cells, bone morphogenetic protein-4 (BMP-4) and Wnt-8. BMP-4 plays a conserved role in patterning the vertebrate dorsoventral axis, whilst the precise role of Wnt-8 and its relationship with BMP-4, are still unclear. Here we have investigated the role played by the GATA family of transcription factors, which are expressed in ventral mesendoderm during gastrulation and are required for the differentiation of blood and endodermal tissues. Injection ventrally of a dominant-interfering GATA factor (called G2en) induced the formation of secondary axes that phenocopy those induced by the dominant-negative BMP receptor. However, unlike inhibiting BMP signalling, inhibiting GATA activity in the ectoderm does not lead to neuralisation. In addition, analysis of gene expression in G2en injected embryos reveals that at least one known target gene for BMP-4, the homeobox gene Vent-2, is unaffected. In contrast, the expression of Wnt-8 and the homeobox gene Vent-1 is suppressed by G2en, whilst the organiser-secreted BMP antagonist chordin becomes ectopically expressed. These data therefore suggest that GATA activity is essential for ventral cell fate and that subsets of ventralising and dorsalising genes require GATA activity for their expression and suppression, respectively. Finally, using G2en, we show that suppression of Wnt-8 expression, in conjunction with blocked BMP signalling, does not lead to head formation, suggesting that the head-suppressing Wnt signal may not be Wnt-8.
在非洲爪蟾中，背腹轴的形成是由腹侧区域的活性信号与斯佩曼组织者分泌的拮抗剂之间的相互作用决定的。在腹侧细胞中有两个信号很重要，即骨形态发生蛋白-4（BMP-4）和Wnt-8。BMP-4在构建脊椎动物背腹轴中发挥着保守作用，而Wnt-8的确切作用及其与BMP-4的关系仍不清楚。在这里，我们研究了GATA转录因子家族所起的作用，这些转录因子在原肠胚形成期间在腹侧中内胚层表达，并且是血液和内胚层组织分化所必需的。向腹侧注射一种显性干扰GATA因子（称为G2en）会诱导形成次生轴，这些次生轴模拟由显性负性BMP受体诱导的次生轴。然而，与抑制BMP信号传导不同，在外胚层中抑制GATA活性不会导致神经化。此外，对注射G2en的胚胎中的基因表达分析表明，BMP-4的至少一个已知靶基因，即同源框基因Vent-2，不受影响。相反，Wnt-8和同源框基因Vent-1的表达被G2en抑制，而组织者分泌的BMP拮抗剂脊索蛋白则异位表达。因此，这些数据表明GATA活性对于腹侧细胞命运至关重要，并且腹侧化和背侧化基因的子集分别需要GATA活性来进行表达和抑制。最后，使用G2en，我们表明抑制Wnt-8表达并结合阻断BMP信号传导不会导致头部形成，这表明抑制头部的Wnt信号可能不是Wnt-8。
