The prepattern transcription factor Irx2, a target of the FGF8/MAP kinase cascade, is involved in cerebellum formation

Ken Matsumoto; Shigeki Nishihara; Mika Kamimura; Tomoki Shiraishi; Takao Otoguro; Masayuki Uehara; Yukiko Maeda; Keiko Ogura; Andrew Lumsden; Toshihiko Ogura

doi:10.1038/nn1249

The prepattern transcription factor Irx2, a target of the FGF8/MAP kinase cascade, is involved in cerebellum formation

Ken Matsumoto, Shigeki Nishihara, Mika Kamimura, Tomoki Shiraishi, Takao Otoguro, Masayuki Uehara, Yukiko Maeda, Keiko Ogura, Andrew Lumsden, Toshihiko Ogura

IDAC - Division of Brain Science

Research output: Contribution to journal › Article › peer-review

85 Citations (Scopus)

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.

Original language	English
Pages (from-to)	605-612
Number of pages	8
Journal	Nature Neuroscience
Volume	7
Issue number	6
DOIs	https://doi.org/10.1038/nn1249
Publication status	Published - 2004 Jun

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@article{b29722c230954adfbce421478cf37024,

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.",

author = "Ken Matsumoto and Shigeki Nishihara and Mika Kamimura and Tomoki Shiraishi and Takao Otoguro and Masayuki Uehara and Yukiko Maeda and Keiko Ogura and Andrew Lumsden and Toshihiko Ogura",

note = "Funding Information: We thank K. Kitamura, J. Aruga, and A. Leutz for probes; and J.L. Gomez-Skarmeta and C.C. Hui for comments. We also thank T. Shimizu and A. Saitoh for assistance. This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas (C) and Creative Basic Research from the Ministry of Education, Science Sports and Culture of Japan, and by the Toray Science Foundation.",

year = "2004",

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doi = "10.1038/nn1249",

language = "English",

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AU - Matsumoto, Ken

AU - Nishihara, Shigeki

AU - Kamimura, Mika

AU - Shiraishi, Tomoki

AU - Otoguro, Takao

AU - Uehara, Masayuki

AU - Maeda, Yukiko

AU - Ogura, Keiko

AU - Lumsden, Andrew

AU - Ogura, Toshihiko

N1 - Funding Information: We thank K. Kitamura, J. Aruga, and A. Leutz for probes; and J.L. Gomez-Skarmeta and C.C. Hui for comments. We also thank T. Shimizu and A. Saitoh for assistance. This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas (C) and Creative Basic Research from the Ministry of Education, Science Sports and Culture of Japan, and by the Toray Science Foundation.

PY - 2004/6

Y1 - 2004/6

N2 - 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.

AB - 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.

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The prepattern transcription factor Irx2, a target of the FGF8/MAP kinase cascade, is involved in cerebellum formation

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