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 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.
Lowell
S
S
Keratinocyte Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Watt
F M
FM
D000199:Actins / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003470:Culture Media; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D011554:Pseudopodia / Q000648:ultrastructure; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014162:Transfection
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003470:Culture Media; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila; D013844:Thiazoles; D053778:Thiazolidines; C064045:delta protein; C037068:latrunculin B; D002118:Calcium