How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development?

Dev Growth Differ. 2004 Dec;46(6):487-94. doi: 10.1111/j.1440-169x.2004.00769.x.


The mesencephalic/rhombomere 1 border (isthmus) is an organizing center for early development of midbrain and cerebellum. In this review, we summarize recent progress in studies of Fgf signaling in the isthmus and discuss how the isthmus instructs the differentiation of the midbrain versus cerebellum. Fgf8 is shown to play a pivotal role in isthmic organizer activity. Only a strong Fgf signal mediated by Fgf8b activates the Ras-extracellular signal-regulated kinase (ERK) pathway, and this is sufficient to induce cerebellar development. A lower level of signaling transduced by Fgf8a, Fgf17 and Fgf18 induce midbrain development. Numerous feedback loops then maintain appropriate mesencephalon/rhombomere1 and organizer gene expression.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cerebellum / embryology*
  • Cerebellum / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / physiology*
  • Mesencephalon / embryology*
  • Mesencephalon / metabolism
  • Mice
  • Molecular Sequence Data
  • Receptors, Fibroblast Growth Factor / metabolism
  • Receptors, Fibroblast Growth Factor / physiology
  • Signal Transduction*
  • ras Proteins / physiology


  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • Extracellular Signal-Regulated MAP Kinases
  • ras Proteins