title: Nuclear translocation of FGF8 and its implication to induce Sprouty2.
abstract: Fibroblast growth factor 8 (FGF8) functions as a local organizing signal for the tectum and cerebellum. FGF8 activates Ras-ERK signaling pathway to induce cerebellar development. We paid attention to the difference in the expression pattern of the molecules that are induced by FGF8 in the mid-hind brain region during normal development and after FGF8 misexpression; some are expressed in the area corresponding to the ERK activation domain but the others are expressed corresponding to the Fgf8 expression domain. Since some of the FGF family members are localized in the nucleus, we wondered if FGF8 could localize in the nuclei and function in the nucleus. We first show that in cultured NIH3T3 cells transfected FGF8b could localize in the nucleus. Transfected FGF8b could also localize in the nucleus of the cells in the chick neural tube. In mouse embryonic neural tube, we detected endogenous FGF8 in the nuclei. Implantation of an FGF8b-soaked bead showed that exogenous FGF8b could be translocated to the nuclei in the isthmus. Furthermore, signal-peptide-deletion mutant of FGF8b mainly localized in the nuclei, and induced Sprouty2 without activating ERK in the mesencephalon. Signal-peptide-deletion mutant of FGF8b could not induce Pax2 expression. Taken together, we concluded that FGF8b could be translocated to the nuclei, and that the nuclear FGF8 could function as transcriptional regulator to induce Sprouty2 in the isthmus.
authors.affiliation: Department of Molecular Neurobiology, Graduate School of Life Sciences and Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, 980-8575 Sendai, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Suzuki
authors.forename: Hidekiyo
authors.initials: H
authors.lastname: Harada
authors.forename: Harukazu
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D018274:Electroporation; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology; D047108:Embryonic Development; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D020540:Metencephalon / Q000166:cytology / Q000196:embryology; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D054259:Neural Tube / Q000166:cytology / Q000196:embryology; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496457:Fgf8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D051524:Fibroblast Growth Factor 8; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse