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EMBO reports 6, 11, 1064–1069 (2005)
doi:10.1038/sj.embor.7400515
AOP Published online: 23 September 2005
Requirement of the MEK5–ERK5 pathway for neural differentiation in Xenopus embryonic development
Satoko Nishimoto, Morioh Kusakabe & Eisuke Nishida
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Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
To whom correspondence should be addressed
Eisuke Nishida Tel: +81 75 753 4230; Fax: +81 75 753 4235; E-mail: L50174@sakura.kudpc.kyoto-u.ac.jp
Received 21 February 2005; Accepted 29 July 2005; Published online 23 September 2005.
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Abstract
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.
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