A Chemical Genomic Approach Identifies Matrix Metalloproteinases as Playing an Essential and Specific Role in Xenopus Melanophore Migration

M.L. Tomlinson; P. Guan; R.J. Morris; M.D. Fidock; M. Rejzek; C. Garcia-Morales; R.A. Field; G.N. Wheeler

doi:10.1016/j.chembiol.2008.12.005

A Chemical Genomic Approach Identifies Matrix Metalloproteinases as Playing an Essential and Specific Role in Xenopus Melanophore Migration

M.L. Tomlinson, P. Guan, R.J. Morris, M.D. Fidock, M. Rejzek, C. Garcia-Morales, R.A. Field, G.N. Wheeler

Research output: Contribution to journal › Article › peer-review

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. © 2009 Elsevier Ltd. All rights reserved.

Original language	Undefined
Pages (from-to)	93-104
Number of pages	12
Journal	Chemistry and Biology
DOIs	https://doi.org/10.1016/j.chembiol.2008.12.005
Publication status	Published - 2009

Keywords

Matrix Metalloproteinase 14
Matrix Metalloproteinases
Metalloproteinase MT1-MMP

Research Beacons, Institutes and Platforms

Manchester Institute of Biotechnology

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10.1016/j.chembiol.2008.12.005

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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. {\textcopyright} 2009 Elsevier Ltd. All rights reserved.",

keywords = "Matrix Metalloproteinase 14, Matrix Metalloproteinases, Metalloproteinase MT1-MMP",

author = "M.L. Tomlinson and P. Guan and R.J. Morris and M.D. Fidock and M. Rejzek and C. Garcia-Morales and R.A. Field and G.N. Wheeler",

year = "2009",

doi = "10.1016/j.chembiol.2008.12.005",

language = "Undefined",

pages = "93--104",

journal = "Chemistry and Biology",

issn = "1074-5521",

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AU - Tomlinson, M.L.

AU - Guan, P.

AU - Morris, R.J.

AU - Fidock, M.D.

AU - Rejzek, M.

AU - Garcia-Morales, C.

AU - Field, R.A.

AU - Wheeler, G.N.

PY - 2009

Y1 - 2009

N2 - 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. © 2009 Elsevier Ltd. All rights reserved.

AB - 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. © 2009 Elsevier Ltd. All rights reserved.

KW - Matrix Metalloproteinase 14

KW - Matrix Metalloproteinases

KW - Metalloproteinase MT1-MMP

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U2 - 10.1016/j.chembiol.2008.12.005

DO - 10.1016/j.chembiol.2008.12.005

M3 - Article

SN - 1074-5521

SP - 93

EP - 104

JO - Chemistry and Biology

JF - Chemistry and Biology

ER -

A Chemical Genomic Approach Identifies Matrix Metalloproteinases as Playing an Essential and Specific Role in Xenopus Melanophore Migration

Abstract

Keywords

Research Beacons, Institutes and Platforms

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