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

Nat Neurosci. 2004 Jun;7(6):605-12. doi: 10.1038/nn1249. Epub 2004 May 9.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cerebellum / embryology*
  • Cerebellum / metabolism*
  • Chick Embryo
  • Chlorocebus aethiops
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / biosynthesis*
  • Fibroblast Growth Factors / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • MAP Kinase Signaling System / physiology*
  • Mice
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Fgf8 protein, mouse
  • Homeodomain Proteins
  • Irx2 protein, mouse
  • Transcription Factors
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors