Lowell S, Watt F M
Keratinocyte Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Mech Dev. 2001 Sep;107(1-2):133-40. doi: 10.1016/s0925-4773(01)00459-2.
In human interfollicular epidermis stem cells lie in clusters surrounded by their differentiated daughters, transit amplifying cells, an arrangement that reflects differences in cell cohesiveness and motility. Keratinocytes expressing a dominant negative Delta1 mutant, Delta(T), lacking most of the cytoplasmic domain, acquired the motile behaviour of transit cells while retaining their stem cell identity. Conversely, overexpression of Delta1 promoted keratinocyte cohesiveness. The adhesive effects of Delta1 and Delta(T) were independent of SuH-dependent Notch signalling. Delta(T) increased motility and spreading of individual keratinocytes and stimulated lamellipodia formation. Delta and Delta(T) colocalised with cortical actin and redistributed on Latrunculin treatment. We propose that Delta promotes keratinocyte cohesiveness by restricting motility and discuss potential mechanisms by which Delta could interact with the actin cytoskeleton.
在人类毛囊间表皮中，干细胞聚集成簇，周围是其分化的子代细胞，即过渡增殖细胞，这种排列反映了细胞黏附性和运动性的差异。表达显性负性Delta1突变体Delta(T)（缺乏大部分细胞质结构域）的角质形成细胞，在保留其干细胞身份的同时，获得了过渡细胞的运动行为。相反，Delta1的过表达促进了角质形成细胞的黏附性。Delta1和Delta(T)的黏附作用独立于依赖SuH的Notch信号传导。Delta(T)增加了单个角质形成细胞的运动性和铺展，并刺激了片状伪足的形成。Delta和Delta(T)与皮质肌动蛋白共定位，并在Latrunculin处理后重新分布。我们提出Delta通过限制运动性来促进角质形成细胞的黏附性，并讨论了Delta与肌动蛋白细胞骨架相互作用的潜在机制。
