Leukotriene synthesis is required for hedgehog-dependent neurite projection in neuralized embryoid bodies but not for motor neuron differentiation

Stem Cells. 2008 May;26(5):1138-45. doi: 10.1634/stemcells.2007-0841. Epub 2008 Feb 21.

Abstract

The hedgehog (Hh) pathway is required for many developmental processes, as well as for adult homeostasis. Although all known effects of Hh signaling affecting patterning and differentiation are mediated by members of the Gli family of zinc finger transcription factors, we demonstrate that the Hh-dependent formation of neurites from motor neurons, like migration of fibroblasts, requires leukotriene synthesis and is different from the Gli-mediated Hh response. Smoothened activity is required for the use of the leukotriene metabolism, and inversely, the leukotriene metabolism is required for mediating the Hh effects on neurite projection. These data establish a function for the previously described arachidonic acid-dependent Hh pathway in a developmentally relevant model system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / pharmacology
  • Cell Differentiation* / drug effects
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / drug effects
  • Embryo, Mammalian / enzymology
  • Enzyme Inhibitors / pharmacology
  • Hedgehog Proteins / agonists
  • Hedgehog Proteins / metabolism*
  • In Vitro Techniques
  • Indoles / pharmacology
  • Kruppel-Like Transcription Factors / metabolism
  • Leukotrienes / biosynthesis*
  • Lipoxygenase Inhibitors
  • Mice
  • Motor Neurons / cytology*
  • Motor Neurons / drug effects
  • Motor Neurons / enzymology
  • Neurites / drug effects
  • Neurites / enzymology
  • Neurites / metabolism*
  • Quail
  • Receptors, G-Protein-Coupled / metabolism
  • Smoothened Receptor
  • Tubulin / metabolism
  • Zinc Finger Protein GLI1

Substances

  • Enzyme Inhibitors
  • Gli1 protein, mouse
  • Hedgehog Proteins
  • Indoles
  • Kruppel-Like Transcription Factors
  • Leukotrienes
  • Lipoxygenase Inhibitors
  • Receptors, G-Protein-Coupled
  • Shh protein, mouse
  • Smo protein, mouse
  • Smoothened Receptor
  • Tubulin
  • Zinc Finger Protein GLI1
  • beta3 tubulin, mouse
  • MK-886
  • Arachidonic Acid