Abstract
ABSTRACTThe 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.
Highlights
Tissue morphogenesis is in balance with cell migration
Loss of Arp3 in the melanocyte lineage causes coat colour defects in mice To assess the role of the Arp2/3 complex in melanoblast migration in vivo, we crossed mice carrying a floxed allele of Arp3 with mice expressing Cre recombinase under the control of the tyrosinase promoter (Tyr::Cre) (Delmas et al, 2003) in a C57BL6/J background (Fig. 1A,B, Fig. S1A)
Histological analysis using the melanocyte marker S100 of postnatal day (P) 14 control skin or skin from black areas of Arp3 fl/ fl Tyr::Cre+ mice demonstrated the presence of melanocytes in the hair follicles, whereas melanocytes were essentially absent from white skin areas of Arp3 fl/fl Tyr::Cre+ mice (Fig. 1E)
Summary
Tissue morphogenesis is in balance with cell migration. During development, cell movements are tightly regulated and highly coordinated in space and time. Handling Editor: Patrick Tam Received 29 June 2020; Accepted 22 September 2020 cells that mainly reside in the bulge of hair follicles in adults, are derived from neural crest cells (Petit and Larue, 2016). Neural crest cells start to migrate from the neural tube around embryonic day (E) 8.5 and the ones that follow the dorsolateral pathway give rise to melanoblasts, the embryonic precursors of melanocytes. From E9.0E15.5, the melanoblast journey begins from the dorsolateral axis towards the developing dermis and involves crossing the basal layer to colonize the epidermis (from E11.5) and reach the first primary hair follicles (from E15.5) (Luciani et al, 2011). Around E13.5 they migrate upward through the dermis and into the epidermis, crossing the basement membrane where they reside in hair follicles (Mayer, 1973; Thomas and Erickson, 2008)
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