Mkp3 is a negative feedback modulator of Fgf8 signaling in the mammalian isthmic organizer

Dev Biol. 2005 Jan 1;277(1):114-28. doi: 10.1016/j.ydbio.2004.09.011.


The pivotal mechanisms that govern the correct patterning and regionalization of the distinct areas of the mammalian CNS are driven by key molecules that emanate from the so-called secondary organizers at neural plate and tube stages. FGF8 is the candidate morphogenetic molecule to pattern the mesencephalon and rhombencephalon in the isthmic organizer (IsO). Recognizable relevance has been given to the intracellular pathways by which Fgf8 is regulated and modulated. In chick limb bud development, a dual mitogen-activated protein kinase phosphatase-3 (Mkp3) plays a role as a negative feedback modulator of Fgf8 signaling. We have investigated the role of Mkp3 and its functional relationship with the Fgf8 signaling pathway in the mouse IsO using gene transfer microelectroporation assays and protein-soaked bead experiments. Here, we demonstrate that MKP3 has a negative feedback action on the MAPK/ERK-mediated FGF8 pathway in the mouse neuroepithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Brain / embryology*
  • Dual Specificity Phosphatase 6
  • Feedback
  • Female
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / analysis
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology*
  • Gene Expression Regulation, Developmental
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred ICR
  • Phosphoprotein Phosphatases
  • Protein Tyrosine Phosphatases / analysis
  • Protein Tyrosine Phosphatases / physiology*
  • Signal Transduction / physiology*


  • FGF8 protein, human
  • Fgf8 protein, mouse
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • Phosphoprotein Phosphatases
  • DUSP6 protein, human
  • Dual Specificity Phosphatase 6
  • Dusp6 protein, mouse
  • Protein Tyrosine Phosphatases