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

Development. 2020 Nov 15;147(22):dev194555. doi: 10.1242/dev.194555.

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.

Keywords: Actin cytoskeleton; Arp2/3; Melanoblasts; Migration; Skin pigmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Animals
  • Cell Adhesion*
  • Cell Line
  • Cell Proliferation*
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Melanocytes / cytology
  • Melanocytes / metabolism*
  • Mice
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Skin / cytology
  • Skin / metabolism*
  • Skin Pigmentation*
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Cdc42 protein, mouse
  • Neuropeptides
  • Rac1 protein, mouse
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein