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.