A chemical genomic approach identifies matrix metalloproteinases as playing an essential and specific role in Xenopus melanophore migration.
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.
Tomlinson
Matthew L
ML
School of Biological Sciences, University of East Anglia, Norwich, UK.
Guan
Pingping
P
Morris
Richard J
RJ
Fidock
Mark D
MD
Rejzek
Martin
M
Garcia-Morales
Carla
C
Field
Robert A
RA
Wheeler
Grant N
GN
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
D000814:Aniline Compounds; D006912:Hydroxyquinolines; D061965:Matrix Metalloproteinase Inhibitors; C539337:NSC 84093; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2