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 MIMP 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.