Fibroblast growth factor 13 is essential for neural differentiation in xenopus early embryonic development

Fibroblast growth factor 13 is essential for neural differentiation in xenopus early embryonic development
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DOI:
10.1074/jbc.m704277200
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发表时间:
2007-08-17
影响因子:
4.8
通讯作者:
Nishida, Eisuke
Nishida, Eisuke
中科院分区:
生物学2区
文献类型:
--
作者:
Nishimoto, Satoko;Nishida, Eisuke

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在非洲爪蟾胚胎发育中,MAPK通路之一的MEK 5-ERK 5通路位于调节神经分化的信号通路中SoxD的下游和Xngnr 1的上游。然而,目前还不清楚MEK 5ERK 5通路在爪蟾神经发育中是如何调节的。由于SoxD是一种转录因子,我们推测SoxD可能诱导某些生长因子并激活MEK 5-ERK 5通路。由于成纤维细胞生长因子13(FGF 13)的表达水平增加的SoxD,我们分析了FGF 13在神经发育中的功能。用反义吗啉代寡核苷酸(MO)敲低FGF 13导致头部结构减少和神经分化抑制。FGF 13 MO抑制SoxD诱导的Xngnr 1表达和Xngnr 1诱导的NeuroD表达,表明FGF 13在神经分化中是Xngnr 1上游和下游所必需的。此外,FGF 13 MO抑制显性阴性骨形态发生蛋白受体(神经诱导物的模拟物)对MEK 5-ERK 5通路的激活,表明FGF 13参与了MEK 5-ERK 5通路的激活。总之,这些结果鉴定了FGF 13在爪蟾神经分化中的作用。
In Xenopus embryonic development, the MEK5- ERK5 pathway, one of the MAPK pathways, lies downstream of SoxD and upstream of Xngnr1 in a signaling pathway regulating neural differentiation. It remains unclear, however, how the MEK5ERK5 pathway is regulated in Xenopus neural development. As SoxD is a transcription factor, we hypothesized that some growth factor should be induced by SoxD and activate the MEK5- ERK5 pathway. As the expression level of fibroblast growth factor 13 ( FGF13) is increased by SoxD, we analyzed the function of FGF13 in neural development. Knockdown of FGF13 with antisense morpholino- oligonucleotides ( MOs) results in the reduced head structure and inhibition of neural differentiation. FGF13 MOs inhibit the SoxD- induced expression of Xngnr1 and the Xngnr1- induced expression of NeuroD, suggesting that FGF13 is necessary both upstream and downstream of Xngnr1 in neural differentiation. In addition, FGF13 MOsinhibit the activation of the MEK5- ERK5 pathway by dominant negative bone morphogenetic protein receptor, a mimicker of neural inducers, indicating that FGF13 is involved in the activation of the MEK5- ERK5 pathway. Together, these results identify a role of FGF13 in Xenopus neural differentiation.