Regulation of isthmic Fgf8 signal by sprouty2.
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.
Suzuki-Hirano
Asuka
A
Department of Molecular Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai 980-8575, Japan.
Sato
Tatsuya
T
Nakamura
Harukazu
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation; D002642:Chick Embryo; D018076:DNA, Complementary / Q000378:metabolism; D018274:Electroporation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008636:Mesencephalon / Q000502:physiology; D020540:Metencephalon / Q000502:physiology; D008954:Models, Biological; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins