CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Institute of Cancer Sciences, University of Glasgow, Garscube Campus, Switchback Road, Bearsden, Glasgow G61 1QH, UK.
Development. 2020 Nov 15;147(22):dev194555. doi: 10.1242/dev.194555.
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 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.
Arp2/3 复合物对于分支丝状肌动蛋白的组装是必不可少的,但它在生理和发育中的作用却出人意料地知之甚少。神经嵴衍生的黑素细胞沿着发育中的胚胎迁移,并穿过真皮到达表皮,殖民皮肤并最终归巢于毛囊内。我们之前已经确定 Rac1 和 Cdc42 指导黑素细胞的迁移。我们假设 Arp2/3 复合物可能是这些小 GTPases 的主要下游效应物。黑素细胞谱系中 Arp3 的耗竭导致小鼠皮肤背部和腹部区域严重的色素沉着缺陷。Arp3 缺失的黑素细胞表现出增殖和迁移缺陷,并且不能像它们的野生型细胞那样伸长。Arp3 在原代黑素细胞中的条件性缺失导致增殖、扩散、迁移和与细胞外基质的黏附不当。总的来说,我们的结果表明,Arp2/3 复合物在小鼠发育中的黑素细胞谱系中是绝对不可或缺的,并表明在需要紧密调节肌动蛋白介导的运动的发育过程中具有重要作用。