Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway
Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway
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DOI：
10.1111/dgd.12254
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发表时间：
2015-12-01
影响因子：
2.5
通讯作者：
Nakamura, Harukazu
中科院分区：
文献类型：
--
作者：
Harada, Hidekiyo;Omi, Minoru;Nakamura, Harukazu
已经表明，强Fgf 8信号激活Ras-ERK信号传导通路以确定后脑，后脑由小脑分化的菱形区1（r1）和峡部（r 0）组成。本研究旨在检测Ets型转录因子Pea 3是否在Ras-ERK信号下游发挥作用，以确定后脑。Pea 3的错误表达导致Otx 2在中脑的表达被抑制，Gbx 2和Fgf 8在中脑的表达被诱导，并且在中脑后部的滋养层神经元分化。未发生顶盖向小脑的命运改变。通过错误表达Engrailed阻遏物结构域EH 1和Pea 3的嵌合分子（eh 1-Pea 3）来抑制Pea 3的功能，导致在后脑中诱导Otx 2的表达，在后脑中抑制Gbx 2和Fgf 8的表达，以及在峡部中眼神经元的分化。由此得出结论，Pea 3在确定Fgf 8-Ras-ERK信号传导下游的峡部（r 0）性质中起关键作用。
It has been shown that strong Fgf8 signal activates Ras-ERK signaling pathway to determine metencephalon, which consists of rhombomere 1 (r1), where the cerebellum differentiates, and isthmus (r0). The present study was undertaken to check if Ets type transcription factor Pea3 functions downstream of Ras-ERK signaling to determine metencephalon. Pea3 misexpression resulted in repression of Otx2 expression in the mesencephalon, induction of Gbx2 and Fgf8 expression in the mesencephalon, and differentiation of the trochlear neurons in the posterior mesencephalon. Fate change of the tectum to the cerebellum did not occur. Repression of Pea3 function by misexpressing the chimeric molecule of Engrailed repressor domain EH1 and Pea3 (eh1-Pea3) resulted in induction of Otx2 expression in the metencephalon, repression of Gbx2 and Fgf8 expression in the metencephalon, and differentiation of the oculomotor neurons in the isthmus. It was concluded that Pea3 plays a pivotal role in determination of the isthmus (r0) property downstream of Fgf8-Ras-ERK signaling.