title: FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals.
abstract: Fibroblast growth factors (FGFs) are signaling molecules of the isthmic organizer, which regulates development of the midbrain and cerebellum. Tissue-specific inactivation of one of the FGF receptor (FGFR) genes, Fgfr1, in the midbrain and rhombomere 1 of the hindbrain of mouse embryos results in deletion of the inferior colliculi in the posterior midbrain and vermis of the cerebellum. Analyses of both midbrain-hindbrain and midbrain-specific Fgfr1 mutants suggest that after establishment of the isthmic organizer, FGFR1 is needed for continued response to the isthmic signals, and that it has direct functions on both sides of the organizer. In addition, FGFR1 appears to modify cell adhesion properties critical for maintaining a coherent organizing center. This may be achieved by regulating expression of specific cell-adhesion molecules at the midbrain-hindbrain border.
authors.affiliation: Institute of Biotechnology, Viikki Biocenter, PO Box 56, 00014 University of Helsinki, Finland.
authors.forename: Ras
authors.initials: R
authors.lastname: Trokovic
authors.forename: Nina
authors.initials: N
authors.lastname: Trokovic
authors.forename: Sanna
authors.initials: S
authors.lastname: Hernesniemi
authors.forename: Ulla
authors.initials: U
authors.lastname: Pirvola
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Vogt Weisenhorn
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Juha
authors.initials: J
authors.lastname: Partanen
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D036386:Ephrin-A5 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins
chemical_list: D015820:Cadherins; C504494:Cdh22 protein, mouse; C080330:En1 protein, mouse; D036386:Ephrin-A5; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D014764:Viral Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; C045073:Cre recombinase; D019426:Integrases