Delta regulates keratinocyte spreading and motility independently of differentiation

In human interfollicular epidermis stem cells lie in clusters surrounded by their differentiated daughters, transit amplifying cells, an arrangement t hat reflects differences in cell cohesiveness and motility. Keratinocytes e xpressing a dominant negative Delta1 mutant, Delta(T), lacking most of the cytoplasmic domain, acquired the motile behaviour of transit cells while re taining their stem cell identity. Conversely, overexpression of Delta1 prom oted keratinocyte cohesiveness. The adhesive effects of Delta1 and Delta(T) were independent of SuH-dependent Notch signalling. Delta(T) increased mot ility and spreading of individual keratinocytes and stimulated lamellipodia formation. Delta and Delta(T) colocalised with cortical actin and redistri buted on Latrunculin treatment. We propose that Delta promotes keratinocyte cohesiveness by restricting motility and discuss potential mechanisms by w hich Delta could interact with the actin cytoskeleton. (C) 2001 Elsevier Sc ience Ireland Ltd. All rights reserved.