The Arp2/3 complex is crucial for colonisation of the mouse skin by melanoblasts

Papalazarou, V., Swaminathan, K., Jaber-Hijazi, F. , Spence, H., Lahmann, I., Nixon, C., Salmeron-Sanchez, M. , Arnold, H.-H., Rottner, K. and Machesky, L. M. (2020) The Arp2/3 complex is crucial for colonisation of the mouse skin by melanoblasts. Development, 147(22), dev194555. (doi: 10.1242/dev.194555) (PMID:33028610) (PMCID:PMC7687863)

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Abstract

The Arp2/3 complex is essential for the assembly of branched filamentous actin, but its role in physiology and development is surprisingly little understood. Melanoblasts deriving from the neural crest migrate along the developing embryo and traverse the dermis to reach the epidermis, colonising the skin and eventually homing within the hair follicles. We have previously established that Rac1 and Cdc42 direct melanoblast migration in vivo. We hypothesised that the Arp2/3 complex might be the main downstream effector of these small GTPases. Arp3 depletion in the melanocyte lineage results in severe pigmentation defects in dorsal and ventral regions of the mouse skin. Arp3 null melanoblasts demonstrate proliferation and migration defects and fail to elongate as their wild-type counterparts. Conditional deletion of Arp3 in primary melanocytes causes improper proliferation, spreading, migration and adhesion to extracellular matrix. Collectively, our results suggest that the Arp2/3 complex is absolutely indispensable in the melanocyte lineage in mouse development, and indicate a significant role in developmental processes that require tight regulation of actin-mediated motility.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Jaber, Dr Farah and Nixon, Mr Colin and Machesky, Professor Laura and Spence, Dr Heather and Papalazarou, Mr Vasileios
Authors: Papalazarou, V., Swaminathan, K., Jaber-Hijazi, F., Spence, H., Lahmann, I., Nixon, C., Salmeron-Sanchez, M., Arnold, H.-H., Rottner, K., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Development
Publisher:Company of Biologists
ISSN:0950-1991
ISSN (Online):1477-9129
Published Online:07 October 2020
Copyright Holders:Copyright © 2020 The Company of Biologists Ltd
First Published:First published in Development 147(22): dev194555
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301636Metabolic drivers of pancreatic cancer cell migration and metastasisLaura MacheskyMedical Research Council (MRC)MR/R017255/1CS - Beatson Institute for Cancer Research
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering