title: A chemical genomic approach identifies matrix metalloproteinases as playing an essential and specific role in Xenopus melanophore migration.
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.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich, UK.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Tomlinson
authors.forename: Pingping
authors.initials: P
authors.lastname: Guan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Morris
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fidock
authors.forename: Martin
authors.initials: M
authors.lastname: Rejzek
authors.forename: Carla
authors.initials: C
authors.lastname: Garcia-Morales
authors.forename: Robert A
authors.initials: RA
authors.lastname: Field
authors.forename: Grant N
authors.initials: GN
authors.lastname: Wheeler
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000201:enzymology; D047108:Embryonic Development; D006801:Humans; D006912:Hydroxyquinolines / Q000737:chemistry / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008547:Melanophores / Q000201:enzymology* / Q000378:metabolism; D012880:Skin Pigmentation; D013329:Structure-Activity Relationship; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D006912:Hydroxyquinolines; D061965:Matrix Metalloproteinase Inhibitors; C539337:NSC 84093; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2