Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo
Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo
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DOI：
10.1242/dev.036715
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发表时间：
2009-11
期刊：
影响因子：
4.6
通讯作者：
Kosuke Tanegashima;Hui Zhao;M. Rebbert;I. Dawid
中科院分区：
文献类型：
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作者：
Kosuke Tanegashima;Hui Zhao;M. Rebbert;I. Dawid
我们将非洲爪哇胚胎发育中的脊索转录组与其他胚胎区域的转录组进行了比较。在原肠胚轴向中胚层中，一大组分泌途径基因在原肠胚早期的脊索中被协调而强烈地激活，而在脊索前体中却没有。编码XBP1和Creb3l2的基因在脊索中也被激活。这两个转录因子与未折叠蛋白反应中分泌途径基因的激活有关，在未折叠蛋白反应中，细胞对内质网未折叠蛋白积聚的压力做出反应。XBP1和Creb3l2在脊索中有差异表达，但没有差异激活。注射反义吗啉可降低XBP1或Creb3l2的表达，导致脊索发育严重不足，但不影响躯体肌肉的发育。此外，注射XBP1吗啉可抑制某些但不是全部分泌蛋白基因的表达。此外，在动物外植体中表达激活形式的XBP1或Creb3l2可以激活类似的分泌途径基因亚集。我们认为，XBP1和Creb/ATF因子介导的一系列分泌途径基因的协同激活是脊索形成的特征和必要特征。
We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation.