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First published online 8 December 2004
doi: 10.1242/dev.01581

Development 132, 257-265 (2005)
Published by The Company of Biologists 2005
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Regulation of isthmic Fgf8 signal by sprouty2

Asuka Suzuki-Hirano1, Tatsuya Sato1,2,* and Harukazu Nakamura1,2,{dagger}

1 Department of Molecular Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai 980-8575, Japan
2 Graduate School of Life Sciences, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan

{dagger} Author for correspondence (e-mail: nakamura{at}idac.tohoku.ac.jp)

Accepted 12 November 2004

Fgf8 functions as an organizer at the mes/metencephalic boundary (isthmus). We showed that a strong Fgf8 signal activates the Ras-ERK signaling pathway to organize cerebellar differentiation. Sprouty2 is expressed in an overlapping manner to Fgf8, and is induced by Fgf8. Its function, however, is indicated to antagonize Ras-ERK signaling. Here, we show the regulation of Fgf8 signaling in relation to Sprouty2. sprouty2 expression was induced very rapidly by Fgf8b, but interfered with ERK activation. sprouty2 misexpression resulted in a fate change of the presumptive metencephalon to the mesencephalon. Misexpression of a dominant negative form of Sprouty2 augmented ERK activation, and resulted in anterior shift of the posterior border of the tectum. The results indicate that Fgf8 activates the Ras-ERK signaling pathway to differentiate the cerebellum, and that the hyper- or hypo-signaling of this pathway affects the fate of the brain vesicles. Sprouty2 may regulate the Fgf8-Ras-ERK signaling pathway for the proper regionalization of the metencephalon and mesencephalon.

Key words: Fgf8, Chick, Sprouty, Isthmus




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