bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish.
bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish.
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发表时间：
2000-06
期刊：
影响因子：
4.6
通讯作者：
Howard I. Sirotkin;S. Dougan;A. Schier;William S. Talbot
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作者：
Howard I. Sirotkin;S. Dougan;A. Schier;William S. Talbot
在脊椎动物胚胎中，母体 (β)-连环蛋白激活建立背轴结构的合子基因的表达。在背轴结构规范中起关键作用的合子作用基因包括同源框基因 bozozok (boz) 和节点相关基因 (TGF-β 家族) 斜视基因 (sqt)。这两个基因均在背侧卵黄合胞层中表达，背侧卵黄合胞层是背侧中胚层诱导信号的来源，突变分析表明 boz 和 sqt 是背侧中胚层发育所必需的。在这里，我们检查了 boz、sqt 和第二个节点相关基因 cyclops (cyc) 之间的调控相互作用。三组证据表明 boz 和 sqt 并行作用，指定背侧中胚层和前神经外胚层。首先，boz 需要 sqt 功能来诱导高水平的异位背侧中胚层，这与 sqt 在 boz 下游或平行作用一致。其次，sqt mRNA 在囊胚期 boz 突变体中表达，表明 boz 对于 sqt 转录的激活不是必需的，相反，boz mRNA 在囊胚期 sqt 突变体中表达。第三，boz;sqt双突变体比boz和sqt单突变体具有更严重的表型。双突变体始终缺乏前神经管和轴向中胚层，腹侧命运显着扩大。在 boz;sqt 突变体中，chordin 和 noggin1 的表达大大降低，表明 boz 和 sqt 途径在激活分泌的 BMP 拮抗剂中具有重叠的作用。与 boz;sqt 双突变体形成鲜明对比的是，boz;sqt;cyc 三重突变体中的前神经命运是特定的。这表明 cyc 抑制前神经发育，而 boz 和 sqt 抵消这种抑制功能。我们的结果支持一个模型，其中 boz 和 sqt 并行作用以诱导背侧化 BMP 拮抗剂并抵消 cyc 在神经模式中的抑制功能。
In vertebrate embryos, maternal (beta)-catenin protein activates the expression of zygotic genes that establish the dorsal axial structures. Among the zygotically acting genes with key roles in the specification of dorsal axial structures are the homeobox gene bozozok (boz) and the nodal-related (TGF-(beta) family) gene squint (sqt). Both genes are expressed in the dorsal yolk syncytial layer, a source of dorsal mesoderm inducing signals, and mutational analysis has indicated that boz and sqt are required for dorsal mesoderm development. Here we examine the regulatory interactions among boz, sqt and a second nodal-related gene, cyclops (cyc). Three lines of evidence indicate that boz and sqt act in parallel to specify dorsal mesoderm and anterior neuroectoderm. First, boz requires sqt function to induce high levels of ectopic dorsal mesoderm, consistent with sqt acting either downstream or in parallel to boz. Second, sqt mRNA is expressed in blastula stage boz mutants, indicating that boz is not essential for activation of sqt transcription, and conversely, boz mRNA is expressed in blastula stage sqt mutants. Third, boz;sqt double mutants have a much more severe phenotype than boz and sqt single mutants. Double mutants consistently lack the anterior neural tube and axial mesoderm, and ventral fates are markedly expanded. Expression of chordin and noggin1 is greatly reduced in boz;sqt mutants, indicating that the boz and sqt pathways have overlapping roles in activating secreted BMP antagonists. In striking contrast to boz;sqt double mutants, anterior neural fates are specified in boz;sqt;cyc triple mutants. This indicates that cyc represses anterior neural development, and that boz and sqt counteract this repressive function. Our results support a model in which boz and sqt act in parallel to induce dorsalizing BMP-antagonists and to counteract the repressive function of cyc in neural patterning.