Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development
Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development
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DOI：
10.1038/sj.embor.7400515
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发表时间：
2005-11-01
期刊：
影响因子：
7.7
通讯作者：
Nishida, E
中科院分区：
文献类型：
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作者：
Nishimoto, S;Kusakabe, M;Nishida, E
虽然以前的研究已经确定了几个关键的转录因子在脊椎动物神经系统的生成过程中，在这个过程中发挥作用的细胞内信号通路仍然不清楚。在这里，我们确定了进化上保守的丝裂原活化蛋白激酶激酶5（MEK 5）-细胞外信号调节激酶5（ERK 5）途径作为神经分化的重要调节因子。用反义吗啉代寡核苷酸敲低爪蟾ERK 5或爪蟾MEK 5导致头部结构减少和神经分化抑制。此外，MEK 5-ERK 5模块自身的强制激活诱导神经分化。此外，我们表明，MEK 5-ERK 5途径是必要的神经化活性的SoxD，神经分化的调节，并足以表达Xngnr 1，一个proneural基因。这些结果表明，MEK 5 ERK 5通路在SoxD下游和Xngnr 1上游的神经分化调节中具有重要作用。
Although previous studies have identified several key transcription factors in the generation process of the vertebrate nervous system, the intracellular signalling pathways that function in this process have remained unclear. Here we identify the evolutionarily conserved mitogen-activated protein kinase kinase 5 (MEK5)- extracellular signal-regulated kinase 5 (ERK5) pathway as an essential regulator in neural differentiation. Knockdown of Xenopus ERK5 or Xenopus MEK5 with antisense morpholino oligonucleotides results in the reduced head structure and inhibition of neural differentiation. Moreover, forced activation of the MEK5 - ERK5 module on its own induces neural differentiation. In addition, we show that the MEK5 - ERK5 pathway is necessary for the neuralizing activity of SoxD, a regulator of neural differentiation, and is sufficient for the expression of Xngnr1, a proneural gene. These results show that the MEK5 ERK5 pathway has an essential role in the regulation of neural differentiation downstream of SoxD and upstream of Xngnr1.