A chemical genomic approach identifies matrix metalloproteinases as playing an essential and specific role in Xenopus melanophore migration

Chem Biol. 2009 Jan 30;16(1):93-104. doi: 10.1016/j.chembiol.2008.12.005.

Abstract

To dissect the function of matrix metalloproteinases (MMPs) involved in cellular migration in vivo, we undertook both a forward chemical genomic screen and a functional approach to discover modulators of melanophore (pigment cell) migration in Xenopus laevis. We identified the 8-quinolinol derivative NSC 84093 as affecting melanophore migration in the developing embryo and have shown it to act as a MMP inhibitor. Potential targets of NSC 84093 investigated include MMP-14 and MMP-2. MMP-14 is expressed in migrating neural crest cells from which melanophores are derived. MMP-2 is expressed at the relevant time of development and in a pattern that suggests it contributes to melanophore migration. Morpholino-mediated knockdown of both MMPs demonstrates they play a key role in melanophore migration and partially phenocopy the effect of NSC 84093.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Animals
  • Cell Movement* / genetics
  • Embryo, Nonmammalian / enzymology
  • Embryonic Development
  • Humans
  • Hydroxyquinolines / chemistry
  • Hydroxyquinolines / pharmacology*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases / metabolism*
  • Melanophores / enzymology*
  • Melanophores / metabolism
  • Skin Pigmentation
  • Structure-Activity Relationship
  • Xenopus laevis / embryology*
  • Xenopus laevis / metabolism

Substances

  • Aniline Compounds
  • Hydroxyquinolines
  • Matrix Metalloproteinase Inhibitors
  • NSC 84093
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2