Regulation and function of FGF8 in patterning of midbrain and anterior hindbrain

Biochem Cell Biol. 2000;78(5):577-84.

Abstract

In this article, an adjunct to a platform presentation at the Winternational 2000 Symposium, we summarize the recent findings of this group concerning the regulation and functions of FGF8 expressed at the isthmus of the developing brain. We show that several different FGF8 isoforms, ectopically expressed in midbrain or posterior forebrain, are able to mimic the proliferative and patterning functions previously attributed to the isthmus in tissue grafting studies. Moreover, we also show that FGF8 protein is sufficient to induce an ectopic isthmic organiser (Fgf-8+, Gbx2+) in anterior midbrain. We also provide evidence that isthmic FGF8 patterns anterior hindbrain, repressing Hox-a2 expression and setting aside a territory of the brain that includes the cerebellar anlage. We show that these effects of FGF8 are likely to be mediated via FGFR1 and be modulated by the putative FGF antagonist, Sprouty2, identified using a differential display screen. Finally, we provide evidence that the onset of Fgf8 expression is regulated by En1 and that its expression at the isthmus is subsequently maintained by a specific and direct interaction between rhombomere 1 and midbrain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Tissue Transplantation
  • Chick Embryo
  • Chimera
  • Coturnix / embryology
  • DNA-Binding Proteins / physiology
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / biosynthesis
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / physiology
  • Mesencephalon / embryology*
  • Multigene Family
  • Nerve Tissue Proteins / physiology
  • PAX2 Transcription Factor
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology*
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / physiology
  • Rhombencephalon / embryology*
  • Transcription Factors / physiology

Substances

  • DNA-Binding Proteins
  • EN1 protein, human
  • Gbx2 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • PAX2 Transcription Factor
  • Protein Isoforms
  • Receptors, Fibroblast Growth Factor
  • Spry2 protein, rat
  • Transcription Factors
  • engrailed 2 protein
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1