title: The prepattern transcription factor Irx2, a target of the FGF8/MAP kinase cascade, is involved in cerebellum formation.
abstract: The cerebellum develops from the rhombic lip of the rostral hindbrain and is organized by fibroblast growth factor 8 (FGF8) expressed by the isthmus. Here we report characterization of Irx2, a member of the Iroquois (Iro) and Irx class of homeobox genes, that is expressed in the presumptive cerebellum. When Irx2 is misexpressed with Fgf8a in the chick midbrain, the midbrain develops into cerebellum in conjunction with repression of Otx2 and induction of Gbx2. During this event, signaling by the FGF8 and mitogen-activated protein (MAP) kinase cascade modulates the activity of Irx2 by phosphorylation. Our data identify a link between the isthmic organizer and Irx2, thereby shedding light on the roles of Iro and Irx genes, which are conserved in both vertebrates and invertebrates.
authors.affiliation: Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University 4-1, Seiryo, Aoba, Sendai 980-8575, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nishihara
authors.forename: Mika
authors.initials: M
authors.lastname: Kamimura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Takao
authors.initials: T
authors.lastname: Otoguro
authors.forename: Masayuki
authors.initials: M
authors.lastname: Uehara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Maeda
authors.forename: Keiko
authors.initials: K
authors.lastname: Ogura
authors.forename: Andrew
authors.initials: A
authors.lastname: Lumsden
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogura
mesh_terms: D000818:Animals; D019556:COS Cells; D002531:Cerebellum / Q000196:embryology* / Q000378:metabolism*; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C496457:Fgf8 protein, mouse; D018398:Homeodomain Proteins; C501596:Irx2 protein, mouse; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors